evolgen archive

The Science Creative Quarterly offers up some tips for purchasing a guard llama. Apparently, this is a legitimate concern, as the author cites five related articles (although I'm not sure if they are real publications, and I'm not ambitious enough to find out for myself). Among the concerns is overqualification (yes, llamas come with different skill sets):

There is nothing worse than an overqualified llama. For instance a llama, trained in the delicate arts of diplomacy, will become depressed and distant if it is only given the task of guarding your ’86 Chevy Cavalier from any would-be vandal. Consequently, it will probably let its guard down and you will be left with a llama with very low self-esteem and an antennae-less ’86 Chevy Cavalier with the words “Wash me” scrawled onto the dirt caked rear windshield.

There's the Onion and Sports Pickle; SCQ may be our equivalent source of science humor.

Republican Fear Factor

2006-01-25T08:48:00.000-05:00

In this week's cartoon, Tom Tomorrow introduces us to Fear Factor, neo-con style. Among the things Republicans are scared of:

They're terrified that their wives could get an abortion without their permission.
They're terrified that their religious beliefs might be undermined by secular society.
They're terrified that heterosexuality itself will be undermined by gay marriage.

It seems obvious to me that these are irrational fears, but it's not obvious to a large portion of this country. These fears manifest themselves in bigotry and oppression of others. Women are denied the right to any abortion regardless of the conditions. Certain religious beliefs (or religion in general) are endorsed by government, and in situations in which everyone is given fair treatment they claim oppression. A loving couple is denied the right to marry because they don't fit what a small minority has deemed the appropriate union (in my opinion, marriage as an institution should not receive government endorsement, but I'm a bit jaded).

A little background on where I stand on abortion: I think that any first trimester abortion should be allowed regardless of the conditions. There should be no restrictions, and they should be easily accessible. Anything after the first trimester should require the woman to show adverse health risks associated with pregnancy. She should not need to jump through loops to show she is at risk, and these abortions should also be easily accessible. I think I stand in the mainstream on this issue.

The last two Republican fears aren’t so easy to mock. One of them is the fear of terrorists. Terrorism is a legitimate concern, although the threat of terrorisms is often blown out of proportion and used to manipulate the general public. The comic isn’t mocking our fear of terrorism, but how the neo-cons use it for their own benefit. They take advantage of the average American's fear that terrorist will blow up their suburban neighborhood. They then use that fear to strip us of civil liberties in the name of anti-terrorism.

As opposed the first three examples (abortion, religion, and gays), it’s not so much the fear of terrorism that is the problem, but the response to that fear. It’s exaggerated and aimed in the wrong direction. We see the same thing in the final fear: “BIRD FLU”. As Tara so nicely pointed out, there may be a rational fear of a pandemic. The paradox is, if immunologists treat it properly (by vaccinating the public and preventing the virus from entering the country), then it appears that all of their work was for not because there was no epidemic. If they fail to act, then the disease may spread and they look like buffoons for not acting. Either way, they lose (there is the possibility that they do not respond and the disease does not spread, in which case they come out on top).

What concern me most are the rational fears to which the administration provides an inadequate response. Abortion, secularism, and gay marriage are important issues, but not nearly as significant as a bungled response to terrorism and pandemic. Of course, if we can’t adequately respond to regular old influence, what makes us think that the response to bird flu will be any better? Maybe it will be used as a scare tactic with no substantive strategy planned in response (see the government’s response to terrorism).

50 People Who Suck

2006-01-24T20:32:00.000-05:00

The BEAST give us the 50 Moast Loathsome People in America. Of note to Clash, Culture, and Science:

46. Bruce Chapman

Charges: Founder of the misnamed “Discovery Institute.” Despite its pioneering title, Chapman’s organization seeks to make one of the world’s oldest, dumbest ideas the prevailing ideology. Seems to believe a petition signed by 400 PhDs and professors is convincing proof of Intelligent Design’s widespread acceptance. A lazy dissembler, he blames the lack of actual research and peer-reviewed articles on ID on academic “blackballing.” Right, ‘cause Galileo had it easy. Chapman’s sole trailblazing achievement in the field of academic inquiry has been in proving scientists can be even smugger-when driven by theology.

Exhibit A: Held high-level positions under Reagan and Bush, Sr. Is not a scientist.

Sentence: Infested and colonized by scabies mites: eyeless, brainless parasites unique to humans—perfect evolved to afflict us. Succumbing to the maddening itch, Chapman skins himself alive.

40. Tom Cruise

Charges: Criminal narcissism. After mega-lawyer Bert Fields threatened to sue The BEAST over Cruise’s inclusion in last year’s Loathsome List, we responded by giving him the editorial finger, and bracing ourselves for the legal spanking of our lives. Instead, the episode seemed to trigger a cascading ego crisis, culminating in a rapid and irrecoverable image downgrade from exalted idol to ridiculous buffoon. From his laughable claim of psychological expertise to his worst acting performance ever—as a man in love—Cruise simply cracked up on camera in 2005, and a public hitherto willing to overlook his obsessively inauthentic personality and comical religious affiliation had finally had enough. Cruise is a perfect example of a person who is simultaneously in love with and completely unfamiliar with himself, living in perpetual fear of self-actualization, and asserting a legal right to live free of criticism. A guy who can do whatever the hell he wants, yet chooses to devote his life to maintaining the public perception that he is somebody else.

Exhibit A: “I care man, I care. I care about you. I care about your children. I care about these people here in this room. Every one of you. And I...I mean it. That is not just some words to me. That is a promise.” Seriously, can’t even act like a human being.

Sentence: A lifetime of forced, joyless sex with famously beautiful women, only to have his colossal gay porn library posthumously bequeathed to the Smithsonian by bitter, unloved offspring.

39. Dr. David Hager

Charges: A Bush appointee to the FDA who was the key figure in its rejection of emergency oral contraceptive Plan B as an over the counter drug, which Hager bragged was the second time in fifty years the FDA has ruled against the overwhelming approval of its own advisory committee. The author of books like Stress and the Woman’s Body and As Jesus Cared for Women, Hager repeatedly sodomized his ex-wife for years against her will, alternately apologizing for or denying it when confronted by her, offering excuses like “You asked me to do that” and “Oh, I didn’t mean to have anal sex with you; I can’t feel the difference,” she told The Nation. Seems a bit fishy, a supposed authority on women’s health who can’t detect such a significant distinction with his most sensitive instrument.

Exhibit A: “My official comment is that I decline to comment.”

Sentence: A three-day group ramming by the multi-dildoed Oregon chapter of NOW, after which Hager will walk with a pronounced limp, never to regain control of his sphincter, and discover himself to be inexplicably pregnant.

37. Donovan McNabb

Charges: Played so poorly that his demoralized and alienated teammates yearned for the return of ego-vampire Terrell Owens. A chocolate commodity so inoffensive he makes Hershey bars look militant. Responded indignantly to loopy criticism from the head of the Philly NAACP, but laughed off Rush Limbaugh’s racist broadsides. Choked in the fourth quarter of Super Bowl; this year he enjoyed the worst fourth quarter passer rating in the league. Made over $11,000,000 in 2004.

Exhibit A: Logged only significant playing time this season with his mom in soup commercials.

Sentence: Peon at a Campbell’s Soup cannery in China. Flogged routinely for underperformance.

33. Johnny Damon

Charges: Any baseball player with highlights in his hair should be faced with the same penalty system applied to those using performance-enhancing steroids. It’s ruining the game. And if a ball player is going to grow a beard, it should be a Charlie Manson/Thurman Munson scraggle of bushy whiskers, not a neatly manicured and softly conditioned frame for your pretty face. The only thing that got Damon to step into line and quit hair-farming was a 52 million dollar check from the New York Yankees. Boston prayed for the multi-bladed Gillette that officially made him a Yankee to slip while gliding over his Adam’s apple and spill his lifeblood into the bathroom sink.

Exhibit A: Going from the Red Sox to the Yankees is like fucking the guy that murdered your husband.

Sentence: Killed by barrage of hurled D cell batteries when he takes the field at Fenway next season.

16. R Kelly

Charges: As if videotaping himself urinating on an underage girl wasn’t bad enough, Kelly decided to follow up by inflicting the worst piece of music in American history upon the public consciousness. Kelly claims he is a genius for squeezing out what are so far 12 installments of his “hip hopera,” “Trapped in the Closet” like so many virtually identical turds, with no variation in musical content and a story line so patently terrible that it soon became the subject of a parody-frenzy involving Saturday Night Live, South Park, Mad TV, Jimmy Kimmel, and the Upright Citizens brigade, among many others. Even his good songs all seem to be about fucking underage girls.

Exhibit A: Seriously—pissing on an underage girl.

Sentence: Trapped in a closet. Eventually dies of thirst.

There are also some good "bend over and fuck me" Democrats, like Hillary Clinton and Joe Loserman, and your usual stable of Republican colostomy bags. Don't miss the surprise at #4.

(via Pale Blue Dot)

Does Being a Horse Count as an Ethnicity

2006-01-24T13:09:00.000-05:00

A high school teacher who happens to be a Pittsburgh Steelers fan (or is he a Steelers fan who happens to be a teacher?) made one of his students take a midterm exam on the floor last Friday because that student was wearing a Denver Broncos John Elway jersey. The kid didn't get the memo: if you're gonna wear a John Elway jersey, go with the Orange Crush look, not the ugly ass angry horsey jersey.

Kid wearing new Broncos jersey (left) and John Elway wearing orange crush jersey (right).

Is Everyone On Earth Named Steve Smith?

2006-01-22T20:05:00.000-05:00

In honor of our favorite punt returner who's quarterback can't get him the ball, here is list of all of the Steve Smith's I know of. Feel free to add more in the comments.

Here's the Carolina Panthers wide receiver (the guy who's quarterback can't get him the ball) and Chad Johnson's junior college teammate that inspired this list. This dude's got a pretty bad-ass tattoo on his upper arm; that distinguishes from the other Steve Smiths. He's the only Steve Smith playing in the NFL (for now), but not the only football playing Steve Smith.

Steve Smith is also the #2 receiver on the USC Trojans. This Steve Smith will be playing in the NFL in two years, only adding to the confusion of players playing the same position with the same name (see here for another example). It doesn't help that USC's Steve Smith is an undersized receiver, meaning not only do Steve Smith and Steve Smith play the same position, they play the same position in the same way.

At least this Steve Smith plays a different sport than the previous two Steve Smiths. Well, technically he no longer plays his sport professionally. Looking at him in the USA Basketball uniform reminds me of how Steve Smith never quite lived up to expectations. This is the opposite of Steve Smith the Panther, who was never supposed to amount to anything, but ended up a pro-bowl quality receiver.

This Steve Smith (actually, Stephen A. Smith) used to be a respectable sports writer. Now he's become a sports talking head and D-list celebrity. Oh, and he writes his columns on a Blackberry. And he's really annoying when he opens his mouth and tries to talk -- not a good quality for a TV personality (but, surprisingly, one that a lot of TV personalities share).

Ok, so Steve Smith is not a real person, but what is "real" anyway? He's a character on American Dad . . . you know, that show that comes on after Family Guy. Never mind.

Weekly Random Ten (22 January 2006)

2006-01-22T18:23:00.000-05:00

New Rules Edition

Alright, we're gonna try something new with the evolgen Weekly Random Ten. Here's the new rule: I get 10 songs worth of time to write an entry. I've used this as a rough guideline for the random ten in the past, but I never put it in writing. Once the last note in the last song is played, I must stop writing -- even if it's in mid sentence.

So, I'm sitting in front of the TV in between playoff games. I blew my pick in the first game. Looks like I went with the wrong road underdog to win. I still think the Panthers can win, but it will be quite a feat if both road dogs win in the conference championship. At least neither Delhomme nor Hasselbeck have a goofy beard -- of course, Hasselbeck's got that bald thing going against him.

I'm gonna do that stupid sports commentator thing and stand by my pick in the second game despite how things have changed. Does that piss anyone else off? An expert analyst will pick a team to win the Super Bowl at the beginning of the season. Then, halfway through the season, the team falls to 4-4, and they're still saying, "I picked them at the start of the season and I'm standing by my pick." That just shows you're too stupid to realize you were wrong and don't know how to reevaluate your position with further evidence. It's bullheaded; it's stupid. At least they're only talking heads (talking about sports, even), and not politicians responsible for making important decisions about the country. It would really suck if politicians were so stubborn and refused to change their stance on an important issue like war in light of new information . . . oh, wait, nevermind. Asshats.

Ok, I've got a couple more songs to kill. How about the size of the American flag that they busted out for the national anthem at the start of the Seahawks game. They love America a lot more than I do. Shit. All that's missing is an F-14 flyover and a huge fireworks display. That would really show those terrorist bastards. Why does the beginning of a sporting event turn into a caricature of patriotism, or even a celebration of a military state. By the way, the Seahawks have the fugliest uniforms ever.

That's enough from me for now. Here are the ten songs I listened to while writing this crappy entry:

Sublime - Get Out!
Gorillaz - Feel Good Inc.
Living End - So What
311 - Light Years
Tilt - Bad Seed
The Hives - A.K.A. I-D-I-O-T
NOFX - Eat the Meek
Jurassic 5 - React
The Ataris - Neilhouse
Pete Townshend - Let My Love Open the Door

Last Second Picks

2006-01-22T12:34:00.000-05:00

It's a few hours before the games begin and here are my picks (see the last edition for how it works):

Pittsburgh Steelers at Denver Broncos
Who I want to win: I'm a Raiders fan, so I hate the Broncos. There is no way I can pull for them. That means that I'm rooting for the Steelers by default. Plus, how can you not be for Troy Polamalu and his hair. And I live in Steelers country, so it's hard to not get sucked into the black and gold fever.

Who I think will win: On a neutral field, the Steelers would win. Too bad this game is being played at ~~Mile High~~ Invesco Field. Broncos will win . . . as long as Plummer doesn't blow it.

Carolina Panthers at Seattle Seahawks
Who I want to win: Ever wonder what a seahawk is? Of course, the Panther is one of the archetypes of conservation genetics. I would be happy to see either of these teams go to the Superbowl. I'm kinda sick of Sean Alexander, though. If Alexander plays well, I wanna see the Panthers win. If Alexander sucks it up big time, go Seahawks.

Who I think will win: The Panthers have won their last five road games (including two playoff road wins). There is no way they can win another road game. There is no way they make it to the Super Bowl. There is no way I'm not picking the Panthers. Yes, the Panthers will win. Plus, when I see someone as tall as I am excelling at receiver in the NFL, I can't help but pull for him.

Enjoy the games.

Sports Reporters

2006-01-22T10:03:00.000-05:00

What the hell was going on with the Sports Reporters this morning? It was like the editor was playing a practical joke on all of us.

Prove It!

2006-01-19T15:21:00.000-05:00

The Quote of the Day goes to Brent Rasmussen of Unscrewing the Inscrutable:

"Proof" is a word that only applies to mathematics and liquor.

I now return you to your regularly scheduled podcast . . .

Haven't You Seen My Movies?

2006-01-16T20:40:00.000-05:00

Something Awful is missing the caption to this image:

There's a motherfucking snake on the motherfucking plane . . . motherfuckers!

YES THEY DESERVED TO DIE!!! AND I HOPE THEY BURN IN HELL!!!

If you don't get it, you need to get it.

One Bourbon, One Scotch, and One Double Black Diamond

2006-01-15T19:05:00.000-05:00

America's favorite drunk-ass skier, Bode Miller (who looks a lot like Edward Burns), has come under fire for boozing while slaloming. Turns out Bode's a drinker with a skiing problem. Slate offers a nice editorial clarifying the whole thing:

Miller tried to clarify his statements, explaining that he didn't actually drink on race mornings, but that, on occasion, he'd arrived at the start with a hangover from the night before.

So, Bode goes out and wins the downhill on Saturday, gets hammered that night, then shows up for the Slalom with some knockin' in his noggin. Sounds ok to me. Rage on Bode, rage on.

More Sunday Afternoon NFL Blogging

2006-01-15T18:02:00.000-05:00

Is this confusing for anyone else?

Adrian Peterson the Chicago Bear (left) and Adrian Peterson the Oklahoma Sooner (right).

One thing that comes with having a good season is increased TV coverage. I've seen a lot more of the Chicago Bears this year (and now in the playoffs), and I've become familiar with some of their players. When I heard that Adrian Peterson was their running back, I thought, "Wow, he wasn't at Oklahoma very long." It turns out there are two Adrian Petersons. In a couple of years, Adrian Peterson, the younger, will be starring in the NFL, only adding to the confusion.

At least the Jason/Jayson Williams had the decency to stand out by playing different positions. Additionally, only Jayson Williams was charged with manslaughter, only one of the Jason Williams has the motorcycle riding skills of Kellen Winslow Jr., and only one of the Jason Williams tokes with Randy Moss.

Why The Patriots Lost

2006-01-15T17:04:00.000-05:00

They didn't give the ball to the Diet Pepsi Machine. Tom Brady threw 36 passes, none of them to the Machine, despite the fact that machine has good hands (what hands?). Let's just hope Pepsi stops running those stupid commercials. Pepsi should take a lesson from Burger King if they wanna incorporate NFL footage into their adds. The latest one with the King as Steve Young is absolute magic (I can't find a link to the ad).

Toni Tony Tone & A Tribute to Troy

2006-01-15T16:13:00.000-05:00

We're all gonna rag on Peyton Manning for losing the game (or Mike Vanderjagt if you hate idiot kickers) -- Manning has never been able to win in college or the pros, providing solid evidence for the Ewing theory when Tee Martin won a national championship at Tennessee after Peyton graduated.

But I'm gonna be a total asshole and claim Tony Dungy should shoulder a lot of the blame. Sure, his son just died. And, yeah, the dude's a man of faith (whatever the hell that's worth). But Dungy's got a bit of Ewing theory going for him, seeing as how the Tampa Bay Buccaneers won a Super Bowl the year after firing Dungy. Dungy deserves some props for turning the Bucs into winners and leading them to the playoffs, but he's gonna be remember as a guy who couldn't win it all.

The Dungy-Manning pairing may make it impossible for the Colts to ever make it to the Super Bowl. The Patriots seemed to be Manning's NFL version of the Florida Gators, but this year (following one of the best starts to season in NFL history) the Colts couldn't even win a single playoff game. It's another year and another flop in the playoffs for Dungy and Manning. I wonder if Dungy never bothered to come back to Indianapolis after his son died or if Peyton got injured while his offensive line could not protect him, would the Colts have fared better in the Playoffs?

So, let's stop treating Dungy like a sacred cow -- the dude's got more choke in him than Michelle Kwan. Yeah, I went there. Whatcha gonna do about it?

Oh, and my boy Troy was all over the place today. Even if he can't catch, the man can defend the pass better than any other safety out there. Don't let anyone cut those Samson locks; his hair is the secret to his power.

Detecting Natural Selection (update)

2006-01-14T23:35:00.000-05:00

I previously remarked that I would be posting my series "Detecting Natural Selection" at Clash, Culture and Science. Well, I changed my mind. The newest installment of "Detecting Natural Selection" has been posted at ScienceBlogs.

Happy Friday the 13th

2006-01-13T07:34:00.000-05:00

It's Friday, January Thirteenth. Don't walk under no ladders. Don't let no black cats walk in your path. And don't shake hands with no lepers.

Ok, I made that last one up.

Fuck You, Rate My Professor

2006-01-12T21:13:00.000-05:00

To anyone who has ever received a poor review on RateMyProfessors.com, you can now stake your revenge at Rate Your Students.

The Best Things Ever Since Anything Ever

2006-01-12T14:34:00.000-05:00

A few things on the internets made me laugh out loud recently. Here they are:

Vince Young's limp wristed throwing style.
Live-action Mike Tyson Punch Out.
How to throw a party in your parents' house when you're home for the holidays.

Maybe the last one isn't that funny, but I wanted to post a link to the first two, and "a few things" sounds better than "two things", and everyone knows you need at least three things to make it a few . . . exemplary run-on, don't you think?

This Is What Happens When You're Culturally Illiterate

2006-01-12T12:19:00.000-05:00

You misread obituaries. Crooked Timber, far more cultured than I, reports that Birgit Nilsson has passed away. Being uncultured, I read it as saying that Brigitte Nielson had died. This would be a very different story. Nilsson was a top soprano in her day (no, not a Soprano, but a singer) hailing from Sweden -- I only learned that from reading her Wikipedia entry.

Birgit Nilsson on the left, and Brigitte Nielson on the right. Notice the differences (ie, Birgit seems to live in some sort of gray-scale world).

Brigitte Nielson, on the other hand, earned fame in the 1980s for her appearance in Beverly Hills Cop II, her marriage to Sylvester Stallone, and her fling with Mark Gastineau. She disappeared (as much as a 6 foot 1 inch, platinum blonde, Dane can disappear) from the limelight until she co-starred in the television opiate, VH1's The Surreal Life. It was during her time on that show that she "fell in love" with Public Enemy's Favor Flave. They then starred in a spinoff show devoted to their disturbing relationship. Apparently, they're splitsville, and Brigitte is planning to marry some guy half her age even though she still hasn't completed the divorce with her previous husband.

Birgit and Brigitte have something in common: both had careers as singers . . . Birgit far more successful and talented.

NFL Playoff Picks

2006-01-11T20:43:00.000-05:00

I promised you more diversity, and now I'm gonna deliver. Today, I give you my way of picking the winners of sporting events. The premise is, a sports fan has the team he thinks is going to win a game and the team he wants to win. Sometimes they are the same team, sometimes they are not (this leads to hedging your bets by laying down money on a team you don't want to win). I got this idea a couple of weeks ago, and I wish I had done it for the wild-card weekend, but I did not. So, here is the first "who I want to win, and who I think will win". Most of the time it comes down to which team I hate the least.

Washington Redskins at Seattle Seahawks
Who I want to win: That's easy: the Redskins. If you paid attention, you'd know that I'm pulling for the racist epithets to go all the way just so I can watch Clinton Portis play dress up. That, and I have a hard time pulling for a bald quarterback.

Who I think will win: The Seahawks will probably win seeing how they have the best running back in the NFL (yes, better than Southeast Jerome), and the 'Skins set the record for fewest yards in a playoff win.

New England Patriots at Denver Broncos
Who I want to win: Neither team. I'm hoping an avalanche buries the city of Denver this weekend, and the game gets cancelled, so the winner of the other AFC divisional game gets an automatic trip to the Super Bowl. I'm sick of the Patriots -- they beat my beloved Raiders in the tuck game. I hate the Broncos (and the Chiefs) because I'm a Raiders fan.

Who I think will win: The fucking Patriots. They always win these games. Even though Denver beat them earlier in the season. Even though Denver had a better regular season. Even though New England has a bunch of injured players. New England will still win.

Pittsburgh Steelers at Indianapolis Colts
Who I want to win: Colts, I guess. The Steelers busted up Carson Palmer's knee. They also knocked off the Bengals, which means no more Chad Johnson touchdown celebrations.

Who I think will win: The Colts have a better defense, a better offense, and home field advantage. They also have a Manning at quarterback, which means look out for the choke. That said, I still think the Colts will win.

Carolina Panthers at Chicago Bears
Who I want to win: I'm apathetic about this one. When in doubt, pull for the underdog. So , let's go Panthers. Besides, if the Bears win, the final score will be 5-3. At least if the Panthers win there's a chance that some points will be scored.

Who I think will win: The Bears are favored, but I think the Panthers will pull it out. The Bears have a great defense and no offense. The Panthers have a solid defense and an ok offense. Unless the Bears D puts up two scores, they ain't gonna win.

There they are, my picks. Let's see how I do.

Evolgen Jumps the Shark

2006-01-11T17:01:00.000-05:00

In a classic episode of Happy Days the Fonz goes water skiing and (in a moment of pure special effects glory) jumps over a shark. It is said that the show was never the same again. Hence, the term “Jumping the Shark” was born to describe the moment when a TV show (or any other pop-culture item) tries some gimmicky trick to lure in viewers because they have run out of good ideas -- see, also, it’s all downhill from here.

In announcing its move to the new Seed Media Group blog consortium, Science Blogs, Dispatches from the Culture Wars proclaimed that Ed is Selling Out, conjuring up images of Pete Townshend and Roger Daltrey hawking deodorant and baked beans on an album cover. I too am moving over to Science Blogs, but while Ed may be doing it for the money, evolgen’s move over to Seed is motivated by sheer masochism. You see, I’m jumping the shark, shooting myself in the foot so to speak.

Don’t expect evolgen to ever be the same again. This humble little blog is movin’ on up to the east side (to a deluxe website in the sky) to live with George and Weezie. You can say that we finally got a piece of the pi (bad, nay, horrible science joke).

Most of the science content of evolgen will be posted at my new Science Blogs url (http://www.scienceblogs.com/evolgen). Bookmark that link, write it down, tattoo it on your ass, or do whatever you need to do to remember my new internet location. But don’t lose this url. My current plan is to continue posting non-science related stuff here at Blogger (and we will maintain this site as an archive of previous evolgen posts) such as the apathetically enjoyed Weekly Random Ten and some stuff on sports and pop culture. While most of the science content will be posted over at Science Blogs, I will keep posting my Detecting Natural Selection series at Blogger.

Given the shift in focus of this blog, and the fact that the Science Blogs site will contain the bulk of the evolution and genetics that make up evolgen, I will be moving the description “AT THE CONVERGENCE OF EVOLUTION AND GENTICS” over to the Science Blogs version of evolgen. The Blogger version of evolgen will now be known as:

Clash, Culture and Science

The name comes from the title of a Rancid song (Cash, Culture and Violence), with some slight modifications. “Clash” refers to the only band that matters, but also the general idea of confrontation, disagreement, and antagonism. You will be seeing more posts on things that piss me off (ala another mad biologist you may be familiar with), and these will not be limited to intelligent design creationism. As you may have noticed, I am a pop-culture whore. You can expect a lot of posts on this guilty pleasure (along with some posts on sports) in the “Culture” section of Clash, Culture and Science. Finally, I would be remiss to leave out any “Science” writing. While the new Science Blogs version of evolgen will have the bulk of the science content, Clash, Culture and Science will also have a science angle.

I’m not the only one to jump the shark (or sell out, whatever the case may be). Here are some friends of evolgen that will be joining me over at Science Blogs:

Dispatches from the Culture Wars
Afarensis
Stranger Fruit
The Intersection
Pharyngula
Gene Expression
Living the Scientific Life

Give the British Some Spare Time . . .

2006-01-11T13:54:00.000-05:00

. . . and they'll give you a neat little web-ap. The author a popular molecular evolution text has heeded the call of E.O. Wilson and created a webpage for every species known to man. He actually didn't make a separate page for each species, but rather created a website that searches three databases for information on a query species: it looks up the taxonomic name for the species on NCBI, searches the web (using Yahoo) to find up to five images of the query organism, and searches Google Scholar for articles related to that species.

The application (known as iSpecies, which I don't think has anything to do with iMac, iBook, iPod, or I, Robot) is available here.

(via Rod Page's blog)

Are Deletions Deleterious? Part 2

2006-01-11T13:28:00.000-05:00

In a previous post I mentioned three recent papers from Nature Genetics that deal with detecting and describing polymorphic deletions using SNPs. I only described the content of one of the papers, as I spent about half of the post trying to give readers some background as to why this is an interesting issue (ie, the idea that deletions are deleterious). In this post I will describe one of the other two papers and, hopefully, formulate some sort of unified idea of why we (by we I mean humans, but these findings should be expected in all other eukaryotes) harbor deletion polymorphisms. I will then add a third (and, probably, final) post on linkage disequilibrium and SNPs.

The approach I previously described uses allele and genotype frequencies to identify clusters of SNPs that are not in Hardy-Weinberg equilibrium. This involves analyzing all of the SNPs in the entire population simultaneously. Another approach, described in the paper from Jonathan Pritchard’s group, uses known relationships of family members (so called “parent-offspring trios”) to identify SNPs that are transmitted from parents to offspring in a non-Mendelian fashion. They start with the observation that individuals carrying a deletion at a SNP locus will appear to be homozygous when genotyped at that SNP (this same assumption was made by Altshuler). They then examined the progeny from the parent-offspring trios for individuals that are homozygous for a particular SNP (note: there will be a lot of homozygous SNPs in any one individual) and see if they could have inherited the same allele from each of their parents. For example, if the parents are genotyped as “AA” and “TT” at a particular SNP, and their child is genotyped as “AA”, either there was a mutation in the germline of the TT parent (changing one of the T alleles to A), or the TT parent is actually “T-“ (where the “-“ means that parent is missing a second copy of the SNP). If one of the parents is T- then the child’s genotype is actually “A-“, and that child inherited the deletion from the parent with the genotype T-.

Figure 1. Examples of four of the seven types of trio genotype configurations used in this analysis.
The true genetic state of each individual is depicted within his or her pedigree symbol. The called genotype, when it differs from the true genotype, is shown outside the pedigree symbol. The three upper configurations (A and C) all result in mendelian incompatibilities. We define 'Type I mendelian incompatibilities' as those that are compatible with a deletion transmitted from parent to child and 'Type II mendelian incompatibilities' as those that are incompatible with the deletion model. Key to figure: A: mendelian incompatibility, genotypes compatible with a deletion transmitted from the mother; C: mendelian incompatibility, genotypes incompatible with a transmitted deletion; E: no mendelian incompatibility, genotypes compatible with a deletion transmitted from the mother (but not the father); G: no mendelian incompatibility, genotypes incompatible with a transmitted deletion. Candidate deletion regions are runs of consecutive SNPs with at least two Type I mendelian incompatibilities and other SNPs that are compatible with a deletion; all the SNPs must suggest transmission from the same parent. See further details in Methods.

Any run of at least two Mendelian inconsistencies was labeled as a deletion. They examined parent-offspring trios from two populations: a European derived population (CEU) harbored 345 deletions and one from Nigeria (YRI) harbored 590. Just like the other paper I described, they validated some of the deletions using quantitative PCR and confirmed that the PCR products from all 12 candidates were in fact valid. They also using an oligonucleotide microarray to test for false positives in 9 of the offspring at 93 deletions and confirmed all but 13 of the deletions (14% false positives). I won’t get into the details of it, but they assessed their power to detect deletions given the amount of polymorphism in the SNP data set, the spacing of SNPs, and the size of the deletions they were identifying.

The median deletion size was 10.6 kb and 8.5 kb in the CEU and YRI samples, respectively, and the size distribution is L-shaped (many small deletions, and a tail containing the large deletions). Most of the deletions were segregating at low frequencies, and 39% were identified in only one trio. Interestingly, some of the deletions at the same locus appear to have different breakpoints, and some deletions sit on multiple haplotype backgrounds, suggesting that certain loci have been deleted independently in multiple lineages. This is nothing new, as many factors (such as repeat sequences flanking a region) can make a particular locus more prone to deletion and duplication (more on this later).

Finally, they took a closer look at deletions that contained genes (exons and introns) and found 267 genes within their entire sample of deleted regions (201 of which were deletions of coding sequence, and 92 were completely deleted genes). There was a deficiency of SNPs in genic regions within deletions compared to genic regions with no association to a deletion, suggesting that purifying selection against haplotypes carrying deletions of genes decreases the variation at these loci. They assigned each gene to a functional class and found an overrepresentation of genes involved in immunity, sensory perception, cell adhesion and signal transduction in their set of 267 deleted genes. These functional classes are similar to those identified in screens for segmental duplications, genes with signatures of positive selection, and lineage specific gene family expansions.

I think the two most interesting finds are the reuse of deletion breakpoint regions (independent origins of the same deletion) and the analysis of functional classes. Many human diseases are the result of the deletion, duplication, or relocation of a particular genomic region. These chromosomal aberrations often occur in somatic cell lines (ie, they are not inherited per se, but the mutation happens some time during the individual’s life history). There is some aspect of heritability when it comes to these types of mutations, as you can inherit a predisposition to a certain genetic disease if you get a defective allele from one parent or you inherit a locus that is predisposed to a deleterious mutation. How can you be predisposed to get a particular mutation? Well, if you have some sort of repetitive sequence (transposable element, segmental duplication, etc) flanking a “disease gene”, that repeat can induce a genomic rearrangement that leads to some deleterious change in that disease gene. The same idea is behind the independent origins of similar deletions that Pritchard’s group proposes.

It appears that certain functional classes of proteins are more prone to rapid evolution, duplication, and deletion. One explanation for the differences in “evolvability” between classes of proteins lies in the differences in purifying selection on different genes. Let’s assume that genes that carry out a more important function than other genes are less robust to mutation (both in amino acid sequence and expression), so that changes to the copy number of particular genes will have deleterious effects. Not only will natural selection remove haplotypes that carry a deletion or duplication of that gene, it will also select against repetitive sequences flanking that gene that would allow for the duplication and deletion events to occur. We see this type of pattern when we look at the location of transposable elements (TEs) in a genome -- they are clustered in intergenic regions, although this may also be due to the effects of TEs on the expression of nearby genes. If only certain genes can withstand having rearrangement inducing repeats in their vicinity, then certain functional classes will be overly duplicated and deleted. Furthermore, some genes (such as large gene families like the odorant receptors) appear to be overly duplicated, suggesting natural selection may favor repetitive sequence near these genes (in fact, duplicated genes alone can spur on more duplication because they are repetitive sequences themselves).

If we imagine that certain classes of genes are under more purifying selection than other classes, then we can expect to see the same types of genes in the rapidly evolving class regardless of how we measure the rate of evolution (nucleotide sequence, segmental duplication, deletion, flanked by repeats, or any other technique). I hope to finish my discussion of SNPs and deletions with my next post in which I will attempt to write about linkage disequilibrium (a subject that gives me trouble).

Conrad DF, Andrews TD, Carter NP, Hurles ME, Pritchard JK. 2006. A high-resolution survey of deletion polymorphism in the human genome. Nat Genet. 38:75-81

Hinds DA, Kloek AP, Jen M, Chen X, Frazer KA. 2006. Common deletions and SNPs are in linkage disequilibrium in the human genome. Nat Genet. 38:82-85

McCarroll SA, Hadnott TN, Perry GH, Sabeti PC, Zody MC, Barrett JC, Dallaire S, Gabriel SB Lee C, Daly MJ, Altshuler DM, & The International HapMap Consortium. 2006. Common deletion polyrmorphisms in the human genome. Nat Genet. 38: 86-92.

Creationist Genome Rearrangements

2006-01-10T15:29:00.000-05:00

Following in the footsteps of John Davison, Disco fan and (bad) IDEA club head honcho Casey Luskin has delved into the genome rearrangements discussion. The premise of his argument (from what I can gather seeing as this guy ain't no Dobzhansky) is that humans and other apes do not share a common ancestor because they differ in chromosome number, and that karyotypic change would have been selectively deleterious. There goes the research plan for my postdoc! Anyway, PZ Myers frisks him pretty good, and I added a comment to Myers's post:

Even an argument about duplication would be bogus because of the amount of substantial duplications segregating in populations as Mendelian variants (aka, not mutations in the germline of the previous generation). Luskin doesn't understand how to distill information - yes, there are deleterious rearrangements, but there are also a whole bunch of (nearly) neutral ones. It's just that there has been an ascertainment bias in discovering fussion/fissions, deletions/duplications, and inversion associated with disease. That bias is now fading with population genomic studies of human variation -- there are a lot of structural differences between two "normal" humans.

For an example of the amount of structural variation in the genome, see here. I've also dealt with this when I wrote about a human inversion under selection. And, don't forget that the Robertsonian fusion is probably not responsible for the incompatibility between chimps and humans. Hell, you can take a chunk out of our genome and it still works ok.

Weekly Random Ten (9 January 2006)

2006-01-09T11:24:00.000-05:00

"Where the Hell am I?" Edition

Football (or "American Football" to my international readers) is a dangerous sport full of high impact collisions and body contortions. The power at which the hits occur is made worse by the impression of invincibility the athletes receive from their heavy padding. The average football player wears a helmet with face mask, shoulder pads, hip pads, thigh pads, knee pads, and a tail bone pad. Additionally, many players choose to wear add ons to their shoulder pads (lower back padding, pads that go around the entire lower torso, pads that extend to the biceps, neck rolls), elbow pads, lower arm padding, and a mouthpiece is required in youth leagues, high school, and college (but not in the professional leagues) to reduce the risk of concussions. All of this equipment makes a player (one who's in good shape) look like the caricature of masculinity -- large head and shoulders, narrow waist, and spandex pants that accentuate the shape of the legs.

As I mentioned, it has been argued that the pads make the players feel invincible, so they hit harder than if they were not wearing any protection (the type of tackling in football differs from that in rugby where the padding is minimal). And, as someone who has worn a football helmet, I can say that they are not very comfortable and actually make minimal collisions feel a lot worse. Additionally, they press up against your forehead in an uncomfortable manner that takes getting used to. The helmets (along with mouth pieces), however, do reduce the chance of a concussion, and the facemask protects your pretty face from getting all mashed up.

Two helmets with the classic design (left two), and one with the new Revolution design (right). Notice the additional area to the right of the earhole in the Revolution.

The modern football helmet is a combination of a plastic outer shell with soft padding (often times air cushioned) inside, and it is held on by a chin strap. The facemask is made up of metal bars coated in rubber (much like a hockey goalie's or baseball catcher's facemask). The design used by most players has been around for decades, but was not constructed to any definitive specifications to reduce the impact of a collision. That has changed with Riddell's Revolution helmet, which was designed to reduce the impact of a collision to the side of the head (the area shown to be mostly responsible for concussions). A medical study has confirmed that the new design reduces the chance of a concussion among high school football players:

"Across the three years of this initial study, the annual concussion rate was 5.4 percent in athletes wearing the Revolution helmet, compared to a 7.6 annual percent rate in athletes wearing standard helmets, representing a 2.3 percent decreased absolute risk of concussion for high school football players. In terms of relative risk, Revolution wearers were 31 percent less likely to sustain a concussion compared to athletes who wore standard football helmets."

With a more intelligent design (sorry, couldn't resist) and evidence to support its efficacy, you'd think that all players would jump at the opportunity to wear this safer helmet. In doing so you'd be forgetting about the machismo and image that go into a football player's wardrobe. Defensive backs and wide receivers (players who do a lot of running) have been known to favor playing without knee, hip, thigh, and tailbone pads because they impede movement. Many professional players don't wear mouthpieces (the single best protection against a concussion), especially quarterbacks who must bark out audibles at the line of scrimmage. It's not uncommon to see a player with his chin strap not fully buckled -- something I can only attribute to style over substance (or safety). That said, it suprises me to watch football games (collegiate and professional) and see so many players still wearing the old design when a superior (or, at least, potentially safer although definitely not more dangerous) helmet is available.

Before I start sounding too much like your mom, let me remind you to wear your mittens because it's cold outside. Now that you know more that you would ever want to know about football padding, here is this week's evolgen Random Ten:

Antiflag - She's My Little Go Go Dancer
The Ataris - 1-2-3-4
Ol' Dirty Bastard - Shimmy Shimmy Ya
Guns N' Roses - Oh My God
Catch 22 - Learning the Truth
No Use For a Name - Best Regards
Less Than Jake - Out of the Crowd
Sonic Youth - Tunic (Song for Karen)
Garbage - Push It
Steppenwolf - Magic Carpet Ride

Separated at Birth?

2006-01-08T21:23:00.000-05:00

That's Chris Mooney (one of the few decent science journalists) and Seth MacFarlane (creator of one of the greatest TV shows of all time). Is it just me, or does Chris (on the left) look an awful lot like Seth (on the right)?

Semester Plans

2006-01-08T19:21:00.000-05:00

A new semester begins tomorrow, and this provides some structure to an academic’s life even if he does not take classes. As an aside, I often have difficulty communicating to those ignorant what exactly a graduate student does if he does not take classes. They ask me if I’m working on my thesis, and I say, sort of. I try to explain to them what “research” means, and how I’m trying to build a collection of findings that will eventually make up my thesis. Anyway, there still is structure to be derived from an academic calendar for those of us who must also teach (or, as I prefer to view it, baby sit the lazy).

Considering the new semester begins tomorrow, now seems as good a time as any to lay out some plans for the upcoming semester. Here are the ten things I need to do before the end of May:

Do some wet lab work (I’ve become quite computational).
Push some flies (see #1).
Write at least one good science blog post a day to make me think about the literature I’m reading (unless there aren’t enough articles published worthy of writing about, a decision that will be determined based on whether I feel like writing a blog post).
Read every article that I’ve downloaded to my hard drive (and put into a folder called “To Read”).
Master Perl, R, and MySQL (just because I’m computational, doesn’t mean I know what I’m doing).
Publish three papers in Nature, one in science, and a couple each in Genetics, MBE, and Evolution (because my CV looks more barren than Gilda Radner . . . too soon?).
Sequence five eukaryotic genomes in my spare time.
Get a stalker.
Derive the grand unifying theory of everything.
Figure out a tenth goal for the upcoming semester.

Too much? Maybe it’s a bit ambitious. The way I see it, at least if I shoot for the moon and miss, I’ll end up in the stars . . . or some bullshit like that.

Find Religion

2006-01-08T11:54:00.000-05:00

The Carnival of the Godless is up. I don't usually advertise this carnival, but I have submitted an entry so I figured I'd reciprocate some of the traffic it's sending over here.

As you may have noticed, there have been a few of non evolution/genetics posts recently (ie, my post on the Rose Bowl and religion featured by the COTG). Does this hint that there is a change on the way? Wait and see. I promise you'll always be able to get your evolutionary genetics from evolgen.

Are Deletions Deleterious? Part 1

2006-01-07T17:09:00.000-05:00

Large scale deletions have been used by geneticists for a long time. A Drosophila geneticist can order a line (a small population of nearly identical flies characterized by some genetic similarity) carrying a deletion for practically any segment on any chromosome (this is only true for D. melanogaster). These so called “deficiency” stocks are useful as they can be used to expose recessive mutations for a particular region of the chromosome (creating hemizygous individuals). They are also used to map the genomic location of recessive mutations, in a process known as deficiency mapping. Overlapping deletions either expose the mutant phenotype or do not, allowing the geneticist to determine the section of the chromosome containing the mutated gene.

Large scale deletions in Drosophila are assumed to be deleterious because they eliminate multiple genes within the deleted region; flies homozygous for these deficiencies probably do not survive to adulthood, and if they do, they most likely suffer major fitness costs. What about smaller deletions? We can assume that the deletion of a coding region (either partial or complete) is probably not appreciated by the organism if the deleted sequence encodes some important protein. Also, if the deletion leads to a frameshift, the encoded protein will be dramatically changed. Many non-coding sequences contain important regulatory elements, the deletion of which is probably ill advised if they control the expression of a vital gene. But many eukaryotic genomes (including all of the mammalian genomes studied) have huge chunks of non-coding DNA, much of it probably not involved in the regulating gene expression.

If we examine a genome, we can identify deletions and determine whether they are more common in coding or non-coding regions. With the influx of whole genome sequences, much has been made about copy number variation in humans. Variation in copy number can be due to a duplication in one genome or a deletion in the other genome. If, however, one genome has a single copy of a sequence and the other genome has no copies, deletion in one genome seems like a very likely scenario. Three papers published in Nature Genetics report the identification of polymorphic deletions in human populations and some analysis of their distribution (for a review of these articles, go here).

David Altshuler’s group (along with the HapMap Consortium) present a single nucleotide polymorphism (SNP) based approach for identifying deletions. Their design is quite elegant and is based on the expected relationship of allele and genotype frequencies at neutral loci. The observed genotype frequencies of a particular SNP in a population can be used to determine the allele frequencies. We can then use the allele frequencies to calculate the expected genotype frequencies under Hardy-Weinberg equilibrium. If the observed genotype frequencies deviate from the expected frequencies, we have too few individuals with a particular genotype and too many with some other genotype. In the case of polymorphic deletions, an individual that is hemizygous (has only one copy of a locus) will appear to be homozygous when a SNP within that deletion is genotyped. If there are an excess of apparent homozygotes (based on the SNP data) clustered in a particular region, we have reason to suspect that there is a deletion of that region segregating in the population.

They identified 541 deletions (507 of which had not been identified previously) ranging in size from one to 745 kilobases long (with an average of 7.0 kb). They confirmed five of the larger deletions using in situ hybridization to chromosomes, and they tested 60 using PCR (51/60 were confirmed). In total, the deletions contained 266 genes that were either partially or entirely located within deleted regions. They used the expression of these genes to determine whether an individual was homozygous for both copies (wild type, normal level of expression), homozygous for the deletion (no expression), heterozygous/hemizygous (half the expected level of expression), and they found that the deletions were inherited according to Mendelian expectations.

Many deletions are associated with diseases and cancers, but others are probably not very deleterious as they are at appreciable frequencies in human populations. While we can expect that deletions that fail to remove coding sequences may be common, it seems surprising to find that some gene deletions are also found in many individuals (additionally, they appear quite old as they are found in different populations). This begs the question, are all of our genes necessary? Do we have certain expendable coding sequences that we can live without? Maybe they were of important at some time in our evolutionary history, but they are no longer needed. Whatever the case may be, there is no single human genome in terms of sequence or structure, only a rough sketch that we all follow, with our own little quirks and idiosyncrasies (this is true for all other species as well). This, of course, leads us to question how much of our phenotypic uniqueness is due to genetic differences, something I am neither qualified nor prepared to discuss.

In a subsequent post I will describe the other two papers.

Conrad DF, Andrews TD, Carter NP, Hurles ME, Pritchard JK. 2006. A high-resolution survey of deletion polymorphism in the human genome. Nat Genet. 38:75-81

Hinds DA, Kloek AP, Jen M, Chen X, Frazer KA. 2006. Common deletions and SNPs are in linkage disequilibrium in the human genome. Nat Genet. 38:82-85

Does God Give A Shit?

2006-01-05T19:00:00.000-05:00

Before we can ask whether God cares about you, me, or anyone else, we should probably determine whether God exists or not. Well, due to limitations in religion (or, Judeo-Christian religion) we can do no such thing as God's existence must be taken on faith. I'm using the European paradigm of religions because 1) that's what I'm most familiar with and 2) most of the crap I hear about God doing something for people comes from the fundy Christian sects. So, let's assume that God exists (whatever God may be). Does he intervene in our daily lives?

This is question is inspired by Mike the Mad Biologist's problem with athletes thanking God (which came while he was praising PZ Myers for his take on God and the West Virginia miner story):

"I realize that many religious people think God directly intervenes in daily events, but I think that's just silly religion (an aside: on a less serious note, I've wondered the same thing about athletes. If you lost, does that mean Jesus wanted you to miss that tackle?)."

If you were under the impression that I was going to philosophize as to whether God gives a shit about you and me, I apologize for misleading you. I just wanted to pose the question and use the words "God" and "shit" in the same sentence. The same thing could have been accomplished by asking whether God takes a shit. You see, I don't even think God exists, so I feel foolish working under the assumption that he does in order to ask whether he cares. Or she cares. Or it cares. Whatever.

Anyway, the real motivation was to point out the foolishness of thinking you won the big game because God was pulling for your team (if you can imagine the classic image of God sitting on his couch with a beer in one hand, a remote control in the other, and a bowl of popcorn in front of him yelling at Mrs. God to shut the hell up, there's less than two minutes left, and the Packers are driving down the field).

As I was walking out of the Rose Bowl last night (yes, I was at the game, and I don't feel like talking about it . . . yet, but there may be a more detailed post in a couple of days after I have had a chance to mull everything over in my head), I happened to be next to a couple of really tall dudes. One of them looked remarkably like former NBA player Sean Rooks. Given that there aren't that many 6'10" guys in the world, I am fairly comfortable assuming that it was, in fact, Mr. Rooks. There were two other tall guys with Rooks, neither of which I recognized.

One of the other tall guys said something along the lines of, "Both USC and Texas were praying hard for a win, I guess the people in Texas just prayed harder." Some girl who was near us, less than half of the size of Rooks and his tall friends, turned around to agree with the tall dude. I shuttered. Anyone who has ever been to the Rose Bowl knows that the stadium is surrounded by Christians hawking their “God loves you, and if you don’t love him back he’s going to make you suffer forever” message along with the largest density of Jews for Jesus on Earth. The giant Christian signage already had me bitching about proselytizers, and then this comment sent me over the edge.

Apparently, the outcome of the game had nothing to do with the fact that Vince Young has super human strength and speed, the mental discipline to avoid mistakes, and has worked his ass off (along with the rest of his teammates) to earn a National Championship. Nope. Maybe Reggie Bush’s ill advised lateral was an act of God -- something beyond Bush’s control. Or Vince Young’s knee touched the ground on Texas’ first touchdown, but the TV in the replay booth suddenly stopped working because God’s got a few C-notes running on the game. All of this happened because the people in the lone star state convinced God to wear a burnt orange #10 jersey. What a douche bag (the tall dude, not Vince Young or God). If I put a shit load of effort into something, I want to be getting the credit for it, not my imaginary super friend.

High School Biology

2006-01-05T13:38:00.000-05:00

PZ Myers (and others) had a different experience in high school biology than I did. When I first arrived in high school I had aspirations of becoming a screen writer (growing up in Los Angeles does that to you). I took biology in 9th grade (freshman year of high school) and found the class easy, but boring; most science and math classes came easy to me growing up because I realized that if I paid attention in class and did the homework, I was guaranteed a good grade (this actually works all the way through college, but in college the "homework" often consists of reading 100 pages from a textbook every couple of days in each of your courses).

But that was biology in my freshman year of high school. I happened to attend a school that offered a ton of Advance Placement (AP) courses (it was a public school as well, which is a rarity). AP courses, for those of you aren't hip with the lingo, are high school courses designed to be taught at an introductory college level (usually taken in 11th or 12th grade). The premise is that these courses will prepare you for college by allowing you to either test out of an introductory level course in college (by scoring well on the AP exam at the end of the year) or make those introductory courses less challenging by exposing you to more of the material before you arrive at college. I also happened to have very competitive friends in high school, and we considered it a challenge to see who could take the most AP courses and score the best on the exam at the end of the year.

That brings me to the second biology course I took in high school -- the one that got me interested in genetics. I had a great AP biology teacher who had an excellent grasp of the material and could present it very clearly. He was well prepared, and often finished his teaching well within the allotted time allowing us to ask questions and begin on our homework assignments. Prior to taking the class, I viewed science as a stagnant collection of facts (of which, there was not much left to learn), but throughout that year I decided that I wanted to be a scientist. It was during the unit on genetics (there was something about transcription and translation that piqued my interest) that I decided I wanted to pursue a PhD in genetics. I even included this fact in my essays for college applications. A lot of kids apply to college planning on becoming a doctor or a lawyer, but how many enter college with the intent of getting a PhD and know in which field that want to pursue it?

I took AP biology my junior year of high school (11th grade), but I wanted to learn more about biology with one year of high school remaining. Luckily, my AP biology teacher also offered a course in marine biology. He had a close relationship with a marine biology lab at UCLA (he had a masters degree, but I’m not sure if it was in education or biology), which meant we not only had access to specimens for observation and dissection, but we also got to do experiments. I guess this requires another bit of clarification. You see, not only was my high school a public school with good academic facilities, it was also located about five blocks from the Pacific Ocean. That meant we could take monthly field trips to the nearby pier to collect samples, take depth and temperature readings, and study the waves and tidal patterns. We would later analyze our data and observe the specimens we collected in our nets (usually planktonic larvae and crustaceans). We also took a special field trip to tidal pools to observe some of the species we had learned about in class.

I am glad I took AP biology in high school because it meant I did not have to take introductory biology in college. Nowadays, introductory courses are affectionately referred to as “weed out” courses for their notorious ability to eliminate a substantial fraction of freshman students from a particular major. After having been a teaching assistant in introductory biology course as a graduate student, I can confidently say that I’m glad I never had to take such a course as an undergrad. I’m not sure if it’s the impersonal feel of one instructor and hundreds of students, or the absolute rush to cover so many aspects of biology in one semester. Whatever it is, it definitely does not stack up to my AP biology course.

Tangled Bank #44

2006-01-04T11:54:00.000-05:00

Tangled Bank #44 has been posted by Afarensis. Lots of good science to read, so get started.

Red State, Blue State, Rose Bowl

2006-01-03T18:56:00.000-05:00

At first glance, the Rose Bowl (College Football's National Championship game this season) appears to be a clash between the prototypical Red State and the ultra-liberal Blue State. The University of Southern California is located in one of the few liberal strongholds remaining in America, despite its Republican governor (who is actually liberal on social issues despite his blind allegiance to the Republican party). The University of Texas, on the other hand, is located in the home state of his holiness, the unquestionable leader of this nation, Commander Cuckoo Bananas.

Upon further inspection, one quickly finds that the red state school is not so red and the blue state school is the prototype of George W's base. I have never been to Austin, Texas, but from how I have heard it described it sounds like an island of reason in a sea of faith. It's supposed to be eco-friendly, tolerant toward alternative lifestyles, and having a large academic institution to flood the city with ivory tower types couldn't hurt either.

I am quite familiar with the USC crowd, however, growing up with a diehard Trojan fan as a parent. The University of California, Berkeley (long known as a liberal center) contrasts nicely with the private school in southern California -- take this jacket designed by a USC fan for the annual game against Cal as an example. While using stereotypes are not a good way to develop an argument, USC is known for attracting very affluent students (although it's hard to imagine they are any more well off than students at other private universities) and looking down on its cross town neighbor, UCLA, for their middle class lifestyle. Hell, even the gay alumns are log cabin republicans -- ok, a sample size of one hardly makes a case.

But wealth is by no means a perfect indicator of political position, and it appears that USC may be becoming more liberal. I'm having a hard time putting my finger on it, but hanging around USC alumni I have definitely noticed a conservative (read, Republican) slant to their politics. California's affluent communities are known for their strong support of the Republican party and probably wield more strength within the GOP than most any red state. It's these people that probably contribute to the conservative image at USC.

Anyway, if you find yourself thinking red state versus blue state while watching The President (Reggie Bush, not George W Bush) try to outrun the Longhorns' speedy defenders, take a second to reconsider which school is red and which is blue . . . ok, one of them is Cardinal and Gold and the other is Burnt Orange, but you know what I mean.

Detecting Natural Selection (Part 6)

2006-01-03T13:21:00.000-05:00

Calculating Nucleotide Sequence Polymorphism

This is the seventh of multiple postings I plan to write about detecting natural selection using molecular data (ie, DNA sequences). The first post contained a brief introduction and can be found here. The second post described the organization of the genome, and the third described the organization of genes. The fourth post described codon based models for detecting selection, and the fifth detailed how relative rates can be used to detect changes in selective pressure. The sixth post dealt with classical population methods for detecting selection using allele and genotype frequencies.

Much of the popular press surrounding recent publications that proclaim to detect natural selection does not adequately detail whether the researchers have identified purifying selection (selective constraint) or positive (aka Darwinian) selection. See here for a particularly poor article that confused the heck out of me (and I claim to understand genome analysis). Recall from our discussion of codon based models for detecting selection that we can distinguish between these two selection regimes, although the codon based models are not very powerful. We can also use relative rates to identify differences in selective constraint between lineages, but it is difficult to differentiate relaxed constraint from positive selection using these analyses. Furthermore, there are a lot of computational biologists interested in identifying highly conserved regions between genomes under the assumption that these sequences are probably under strong purifying selection.

But what if we’re interested in finding signatures of positive selection? In my opinion, the best data for this type of analysis is DNA sequence polymorphism. This post will detail some of the core concepts in calculating polymorphism from DNA sequences. Subsequent posts will detail the statistical analyses that can be performed on this data.

Signatures of selection can be detected using either protein coding or non-coding DNA; the statistical techniques differ for analyzing these two types of sequences, but the initial steps are very similar. We will refer to region of the genome we are sequencing as a locus. The length of this region can range anywhere from about 500 nucleotides to thousands of nucleotides (the longer the region, the more work the grad student or undergrad doing the lab work must put in). Once a researcher has chosen a particular locus (either because they know sequencing it will be feasible or because it is a near a gene of particular interest), she will sequence it in approximately 20-30 individuals from some population (although it is common to sequence in as few as 10 or as many as hundreds of individuals). Choosing which individuals to sample (and which populations to sample from) is beyond the scope of this entry and often depends greatly on the natural history of the species in question.

DNA alignment. Click on the image for a larger version.

Once all of the “wet-lab” work is completed (which can take weeks if you are lucky or years if you chose a poorly studied taxon and tricky locus), the sequences must be aligned (see above). To read the alignment above, you need a quick primer on the nomenclature. The column on the left contains the identifiers (or names) of the sequences. The first set of sequences is the alignment of the first 50 nucleotides from the locus, followed by numbers that indicate the position of each nucleotide. Below that, we have positions 51-100, then 101-150, etc. Ideally, we would have all the positions aligned in a single block, but the limitations of printed paper prevent such a representation. The color coding is just there to make distinguishing the nucleotides from each other.

I will assume we have a good alignment, although the alignment process can be quite tricky. Each homologous nucleotide can be compared between all of the sequences in an alignment. Sites at which all sequences have the same nucleotide (position 1 above, where all sequences have a G) are monomorphic. If there are different nucleotides at a site (position 6, where some sequences have a C and the others have a T), that site is said to be polymorphic. We can count the number of sites that are monomorphic and the amount that are polymorphic.

We will discuss two types of polymorphism. The first, the number of segregating sites (S_n), is just the amount of polymorphic nucleotide sites in the data set. As the number of sequences in the data set increases, so too do the number of segregating sites. If this is not obvious to you, imagine we have sampled five sequences from a population (if you need a picture, imagine it’s the first five sequences listed above: D_yakuba, RPU74073, RPU74053, PSU74068, TJU74075). We can calculate the number of segregating sites using these five sequences, and this number will usually be less (and never be more) than if we added five more sequences to our sample. Each time we add a sequence, we identify more segregating sites, although there are diminishing returns as more sequences get added -- eventually (ok, after a really long time) you identify all of the segregating sites in a population, and adding more sequences will only result in adding the same polymorphic sites that you have already identified.

The number of segregating sites depends on the number of sequences in your data set, and we will need to apply a simple correction to take this into account (I will address this in a later post). The second type of polymorphism, the average pairwise differences (p), does not suffer from this problem. To calculate p we must first compare all pairwise combinations of sequences in the data set (compare the first sequence to the second, the first to the third, the first to the forth, all the way to the second to the last and the last). In each pairwise comparison we calculate the number of nucleotide sites that differ between those two sequences. Once we have calculated the number of differences between each pair, we divide by the number of comparisons made to get the average pairwise differences. Because we are taking an average, this estimate of polymorphism does not depend on the number of sequences in the sample.

In future posts we will discuss the theoretical framework behind detecting selection using nucleotide polymorphism and how our two estimates of polymorphism can be used to detect natural selection.

Dig Your Way to China

2006-01-02T13:26:00.000-05:00

Or, in my case, dig your way to the Indian Ocean. In case you've always wondered, "If you a dig a very deep hole, where will you end up?" there is now a Google Maps based web application to help you figure it out. The page is written by a Brazilian student, so the English is a bit sloppy, but the concept is kinda cool. To dig your way to China you would have to start in Argentina or Chile.

Weekly Random Ten (1 January 2006)

2006-01-01T19:30:00.000-05:00

Long Live Southeast Jerome Edition

America's favorite team named after a racist epithet has qualified for the NFL playoffs. By defeating the Philadelphia Eagles, the Washington Redskins are now guaranteed one more game, next week against the Tampa Bay Buccaneers (injuns versus pirates!). We are also guaranteed at least one more of Clinton Portis's alter egos.

For those of you who have not been following the best sports story of the fall, please allow me to bring you up to speed. Every Thursday, the NFL requires players to meet with the media and answer questions. In a moment of divine inspiration, Redskins' running back Clinton Portis decided to dress up in what can be best described as costumes stolen from Bootsy Collins's closet for his interview sessions. These were usually solo affairs (although he did employ a teammate to pantomime his arms in one bit), but he brought out a whole gang of teammates when he met with the media last Thursday.

Now that he knows the Redskins will be playing again next week (and he will be holding his weekly press conference on Thursday), I can imagine Portis sitting in his crib debating whether to dress up as Billy Willy Freak-a-dilly or Chief Hoozawoozadoo. I'm gonna be rooting for the 'Skins in the playoffs, not only to see Portis's weekly costumes, but also in the hope that they make the Super Bowl and he brings out the greatest of his bits for the ridiculously overhyped media day.

With all the attention Chad Johnson's been getting for his endzone celebrations (which, by the way, are nowhere near as entertaining as the Icky Shuffle), it's only natural to pull for the Cincinnati Bengals to make the Super Bowl to see what Johnson pulls out for the big game. Imagine Clinton Portis dressed up at media day and Chad Johnson scoring a touchdown and busting out the king of all celebrations. It's enough to make a sports fan forget about steroid allegations, player lockouts, and fat white dudes.

So, put on your biggest pair of goofy glasses, your favorite cape, and come up with a silly nickname. Here's your evolgen Random Ten:

Offspring - Jennifer Lost the War
Mad Caddies - Villains
U.S. bombs - In & Out
Buffalo Springfield - For What It's Worth
311 - Running
88 Fingers Louie - State
Pearl Jam w/ Neil Young - Keep on Rocking in the Free World
Blink 182 - Does My Breath Smell?
Mike Ness - Once a Day
Unwritten Law - Cailin

Divine Design

2006-01-01T18:45:00.000-05:00

Utah Senator Chris Buttars, no relation to Leopold "Butters" Stotch, shown above, wants his own favorite flavor of creationism taught alongside biology in public school science classes. He calls it "Divine Design", which conjures up images of overweight drag queens:

I wonder if Buttars knows that there is already a show on Home & Garden Television by the same name?

The Toilet Seat Debate Settled

2005-12-31T04:13:00.000-05:00

The Science Creative Quarterly, never one to disappoint, has a mathematical treatment of the great toilet seat debate. If you live with a member of the opposite sex and share a single bathroom, a derivation is given to determine who should put the toilet seat up/down and when. It concludes by suggesting:

"In the morning John leaves the seat up after performing #1. In the evening he puts it down.
"This rule may not be precise but it is simple and approximately equitable; moreover the use of a definite rule sets expectations. The seat is put down in the evening to avoid the notorious 'middle of the night surprise'."

This, of course, assumes that middle of the night surprise consists of "her falling in". While this is an obvious concern, the middle of the night mistake is not to be ignored, wherein he forgets that the toilet seat is down and attempts to perform #1. I caution anyone who attempts to apply this model to their home restroom use that us men are notorious for our poor aim, and it is highly advisable to give us a larger target at which to shoot.

Molecular Creationism

2005-12-28T20:23:00.000-05:00

Sahotra Sarkar has a post up at the Post-Genomics blog on why creationists have been targeting molecular biology (an extremely developed field) rather than other fields, such as evo-devo (which has produced very little scientific output relative to more established areas). It's a good read, and Sarkar does a nice job of incorporating where the Disco PR machine falls into this decision.

Update (12/30/2005): Sarkar's post has been deleted, but a cashed version is available here.

Why Study Speciation Genes?

2005-12-28T18:57:00.000-05:00

I mentioned previously that John Wilkins has gotten me thinking about speciation, and his most recent post on speciation contains a bit of a poke at geneticists studying speciation:

“Some researchers, such as Chung-I Wu . . . seek to find ‘speciation genes’ which are modified through this inadvertent selection. This is, I believe, a category mistake, and a logical fallacy.

”The category mistake is to presume that because a genetic distance causes speciation, it is therefore a gene ‘for’ speciation. But there is no prior specification of genes that cause reproductive isolation. A genetic change may do so, or it may not. Identifying that it has done so is something that can only be done post hoc. And there appears to be no particular genes that cause speciation over large evolutionary distances - there may be an active gene complex in Drosophila which when changed causes reproductive isolation, but it doesn't therefore follow that a homolog of that complex will do the same thing in other flies, or in insects generally, or in all animals, etc. In fact, it doesn't even follow that we will find this is the complex involved in all cases of Drosophila speciation, either.”

I will argue that Drosophila geneticists are not so much interested in finding “speciation genes”, but rather interested in understanding the genetics of speciation. To do so requires finding mutations that allow the species boundary to be surmounted. As I have mentioned previously, good species are reproductively isolated, preventing any genetical analysis of the factors that lead to this isolation. Mutations in the “speciation genes” (especially the extremely useful Hybrid Male Rescue mutation), however, allow researchers to cross individuals from different species and study the genetics of speciation.

Geneticists like to find generalities. That is why we study model organisms; they are easy to work with in a laboratory setting and allow us to extend our discoveries regarding molecular biology, cellular function, development, physiology, etc to other related taxa (both closely related and more distant relatives). Wilkins makes a valid point that it is difficult to generalize discoveries regarding the genetics of speciation made within one system (compared to the generalizing done in other fields). For example, finding a speciation gene in one species pair does not say anything about that gene’s involvement in speciation in general. I don’t think you will find a single geneticist who would disagree with that.

Other research on the genetics of speciation does provide the potential to generalize across different taxa (finding these “speciation genes”’ is merely a necessary step in this process for some species pairs). It is difficult to say how common certain patterns are in speciation, but some of the following insights from Drosophila have the potential to be applicable in distantly related taxa.

Researchers have shown that genome rearrangements can influence the distribution of genes responsible for reproductive isolation throughout the genome between sympatric and parapatric species pairs. Some have argued for the same type of relationship between chromosomal inversions and speciation in humans and chimps, but they may have done the analysis incorrectly or even violated one of the assumptions of their model (humans and chimps probably speciated allopatrically). The findings in Drosophila are similar to those observed in Rhagoletis and in sunflowers, suggesting that this model may be common for parapatric speciation.

With the development of high throughput technologies for studying genome wide patterns of gene expression in Drosophila, researchers have begun to investigate expression changes in species hybrids. The disproportionate effect of cis regulatory changes between species pairs (compared to trans changes) has not been tested outside of the D. melanogaster species group. This type of find differs from the discovery of a “speciation gene” because it is a trend observed from the study of a large set of genes mis-expressed in species hybrids. These experiments would not be possible without the use of speciation gene mutants so that interspecific hybrids could be created.

Wilkins will be happy to know that some researchers are interested specifically in finding which genes are involved in maintaining species boundaries. They do so not for the sake of finding the genes, but for determining how those genes evolve. Some focus on the role of natural selection in speciation. Many others are interested in understanding how genetic changes between species lead to behavioral differences that underlie the prezygotic isolation of the species. And yes, some do study individual speciation genes, but they do so to understand why natural selection would favor the evolution of a particular protein and how it interacts with other gene products to prevent interspecific hybridization.

While the individual genes responsible for speciation may not be the same between different species pairs, “speciation genes” are probably under the same evolutionary forces regardless of which species pair one studies. As researchers discover more speciation genes, it will become possible to determine if certain classes of proteins (such as transcription factors) are disproportionately present within the catalog. Biologists do not study the genetics of speciation simply to find speciation genes; they search for speciation genes (and QTLs) to determine how organisms, the environment, and the genome interact to produce reproductive isolation between species.

Detecting Natural Selection (Part 5)

2005-12-24T13:36:00.000-05:00

Allele and Genotype Frequencies in Populations

This is the sixth of multiple postings I plan to write about detecting natural selection using molecular data (ie, DNA sequences). The first post contained a brief introduction and can be found here. The second post described the organization of the genome, and the third described the organization of genes. The fourth post described codon based models for detecting selection, and the fifth detailed how relative rates can be used to detect changes in selective pressure

The previous analytical techniques we have discussed all deal with comparing sequences from different species (or homologous sequences that resulted from gene duplication). From here on out we will be discussing how variation within a species can be used to detect natural selection at the sequence level. To do this we must first address what we expect when there is no selection. This post deals with expected allele and genotype frequencies and changes in allele frequencies between generations (something I have written about before). Subsequent posts will use more recently developed analyses that allow us to detect selection by sampling allele frequencies in a population.

Before we begin discussing how to detect natural selection we must lay out our neutral expectation (ie, null hypothesis). Let’s begin by assuming a one locus, two allele model, where the two alleles are given by A and a. We can use a Punnett square to determine the expected frequency of each genotype in a mating between two heterozygotes.

	A	a
A	AA	Aa
a	Aa	aa

We expect one quarter of the progeny to have the genotype AA, one quarter to have the genotype aa, and half to be heterozygous (Aa). We can extend this model to determine the expected genotype frequencies in a population after one generation of random mating. Let the frequency of allele A in the first generation be p, and the frequency of allele a is given by q (p + q = 1).

	p	q
p	p²	pq
q	pq	q²

As you can see from this table, when there is random mating, a large population, no mutation, no migration, and no natural selection, the genotype frequencies in the second generation can be given by the following equations (in terms of allele frequencies in the previous generation):

Freq(AA) = p²
Freq(Aa) = 2pq
Freq(aa) = q²

We can then use these formulas to determine the allele frequencies in the second generation. Let p' and q' be the allele frequencies of A and a in the second generation, such that:

p' = p² + pq
q' = q² + pq

As I have previously described, Hardy and Weinberg showed that random mating on its own does not change allele frequencies. We can see that by rearranging the equation for p' given above:

p' = p(p + q)

As mentioned above, p+q =1, so p' = p, and we have proof that random mating alone does not alter allele frequencies (the frequency of allele a does not change because q' = 1-p', which is equivalent to q'=q).

Natural selection, however, can lead to changes in allele frequencies between generations. I detailed how to determine the expected allele frequencies after selection given the allele frequencies before selection and the fitness of the different genotypes in my post on mean fitness and genetic load. We can also derive the marginal fitness of the alleles (remember, fitness is a measure of the number of progeny left per individual carrying a particular genotype, and in diploid organisms the genotype consists of two alleles), and we get the following results:

W_A = pW_AA + qW_Aa
W_a = qW_aa + pW_Aa

where W_A and W_a are the marginal fitnesses of alleles A and a, and W_AA, W_Aa, and W_aa are the fitness of each of the genotypes (the number of progeny left by an individual carrying that genotype). As you can see, by measuring changes in genotype frequencies from generation to generation we can estimate the fitness of each genotype, and by measuring changes in allele frequencies we can estimate the marginal fitness of each allele.

These results provide the theoretical framework for all of population genetics, but they are rarely used to detect selection because more powerful techniques have been developed for molecular data. I still felt it necessary to lay out some of these concepts for you so that you can appreciate what will follow: detecting natural selection using nucleotide sequence polymorphism.

On Bullshit

2005-12-24T12:36:00.000-05:00

I just finished reading Harry G. Frankfurt's On Bullshit -- well, "finished" is a bit of a misnomer, as it was more like started and finished within an hour. It's a fun read, but not really worth the $10; it's hard to justify charging that much for a clever essay (not to mention the absurdity of binding a single essay as a hard cover book).

Frankfurt, an emeritus professor of philosophy at Princeton, inspired by the amount of bullshit spewed forth in modern society, sets out to determine what makes a statement bullshit. He concludes that something is bullshit when a person makes a declaration with no regard to the known facts and current evidence (whether or not they think they are lying is irrelevant). Does this remind you of anything or anyone? I found one particular passage quite fitting given the recently concluded proceedings in Dover:

"Bullshit is unavoidable whenever circumstances require someone to talk without knowing what he is talking about. Thus the production of bullshit is stimulated whenever a person's obligations or opportunities to speak about some topic exceed his knowledge of the facts that are relevant to that topic. This discrepancy is common in public life, where people are frequently impelled -- whether by their own propensities or by the demands of others -- to speak extensively about matters of which they are to some degree ignorant."

How to Tell When People Don't Respect Your Field

2005-12-24T11:30:00.000-05:00

Take that Cosmic Variance:

Weekly Random Ten (23 December 2005)

2005-12-23T20:34:00.000-05:00

Last Random Ten of the Year Edition

With Christmas, Chanukah, and New Years going on, I won't have time to post another Weekly Random Ten before the year is out; you can consider this post a wish of happy whatever the hell it is you're celebrating this year. Unless it's Kwanzaa -- that's not a real holiday. If it was, I'd wish you a Killer Kwanzaa.

Happy Festivus to the rest of us. Now, go drink some egg nog, exchange secular holiday season presents, and remember why you only see your family once a year. Oh, and here's your evolgen Random Ten:

Tilt - Berkeley Pier
Fifteen - Landmine
Me First and the Gimme Gimmes - Fire and Rain
Wu-Tang Clan - Gravel Pit
The Von Bondies - Crawl Through the Darkness
Coheed & Cambria - The Crowing
The Bouncing Souls - Born to Lose
Elton John - Rocket Man
Jimi Hendrix - Purple Haze
88 Fingers Louie - Two Face Bastard

Too Much Law, Not Enough Science

2005-12-23T19:51:00.000-05:00

While everyone is engaged in an orgy of Kitzmiller v Dover legal babble, I'd like to write about some actual science. After a few days of an unreliable internet connection (traveling to see family), I'm finally staying with someone with a fast connection that I can plug in to (well, that wasn't meant to be a double entendre). I'll hopefully have some posts up over the next few days. John Wilkins has been writing some good stuff on speciation that has inspired me. While he prefers the philosophical aspects, I may delve into some of the more experimental analyses on the genetics of speciation. I will also get back my Detecting Natural Selection series, moving on to population genetics.

And, here's a little teaser for you: expect some changes to evolgen in the new year . . .

In Case You Didn't Hear . . .

2005-12-20T11:35:00.000-05:00

. . . Intelligent Design is out.

I don't think I'll have much else to say about this. As you can see by my recent posts, I'm trying to focus this blog toward science (and ski jumps, television, and bad journalism). Mostly science, though.

Update (21 Dec 2005): The Questionable Authority has posted a roundup of commentary on the Dover decision. Blogarithmicly has some links as well.

Mean Fitness, Genetic Load, and the Misapplication of Population Genetics Metrics

2005-12-20T08:56:00.000-05:00

I will probably deal with some of these concepts in my Detecting Natural Selection series, but a couple of letters in the American Scientist (hat tip: Deinonychus antirrhopus) have inspired me to post my opinion. The letters -- one a reply to an article by Paul E. Turner, and the other a reply by Turner to the first letter -- deal with how natural selection shapes the fitness of individuals and populations. In the first letter, Dmitri E. Kourennyi complains:

"In the last paragraph of the 'Cheaters Sometimes Prosper' section, the author mentions an apparent conflict between the prediction of evolutionary game theory in the prisoner's dilemma and the theory of evolution. Cheaters can lower the average fitness of the population. On the other hand, paraphrasing the author's statement, Darwin's theory of evolution suggests that the population becomes better adapted to its environment over time.

"As far as I know, evolutionary theory does not claim that populations are driven toward higher fitness. Evolutionary pressure acts at the level of individuals. As a result, the average fitness of the population usually increases, but it can decrease in some cases, such as when cheaters have an advantage over cooperators and can take over the population."

To which Turner replies:

"In my opinion, Dr. Kourennyi is misreading this sentence in at least two ways. First, his literal reading is that 'steers' is equivalent to 'guides,' where the population is purposefully taken in the direction of increased fitness. As he correctly indicates, natural selection is blind and the process does not drive populations to increased fitness through time. As for Dr. Kourennyi's conclusion, I wrote that '[Prisoner's dilemma] is somewhat counter to Darwin's theory by natural selection.' Selection can favor takeover by cheaters, leading to a surprising (in a Darwinian sense) decrease in mean fitness of the population."

I think they’re both pissing into the wind on this one, as there is no meaningful way to measure the fitness of a population (someone can correct me on this, but please read below for my argument). The two measures I usually equate with population fitness are mean fitness and genetic load. Mean fitness, however, does not have any meaning outside of the context for which it was derived -- as a factor used in determining the expected change in allele frequencies under natural selection. Genetic load, which is calculated using the meaningless statistic mean fitness, is therefore a useless metric.

Let us first examine mean fitness. Under Hardy-Weinberg equilibrium allele frequencies remain constant from generation to generation and can be used to predict the genotype frequencies. If we have a one locus, two allele system (alleles A and a), where the frequency of A is given by p and the frequency of a is given by q (and q = 1 - p), we get the following genotype frequencies:

Freq(AA) = p²
Freq(Aa) = 2pq
Freq(aa) = q²

Now, imagine that one genotype is more fit than the others (leaves more offspring per individual carrying that genotype), so we get the following fitness measurements for each genotype: W_AA, W_Aa, W_aa. The fitness of a genotype can be thought of as the number of offspring left per individual carrying that genotype, such that W_AA is the number of offspring from an AA individual. To standardize for differences in the number of individuals carrying each of the three genotypes and the fitness of the different genotypes relative to each other, we use the mean fitness:

W_bar = p²W_AA + 2pqW_Aa + q²W_aa

The frequency of each genotype after selection can be calculated using the frequency of each genotype before selection, the fitness of that genotype, and the mean fitness:

Freq(AA after selection) = p²W_AA / W_bar
Freq(Aa after selection) = 2pqW_Aa / W_bar
Freq(aa after selection) = q²W_aa / W_bar

By favoring particular genotypes, natural selection leads to changes in allele frequencies between generations. The frequency of the A allele can be calculated using the frequency of the genotypes carrying that allele:

p = Freq(AA) + ½Freq(Aa)

If we represent the frequency of the A allele before selection as p and after selection as p', we get the following:

p' = (p²W_AA / W_bar) + ½(2pqW_Aa / W_bar)

This model can be applied to any locus regardless of the number of alleles segregating at that locus (I’ll leave it up to the reader to perform this derivation).

As you can see, W_bar is simply a metric used to account for the fitness of each genotype relative to each other, and is used when we would like to calculate changes in allele and genotype frequencies due to natural selection. It is called “mean fitness”, but it does not measure any meaningful aspect of the population. This did not stop J.B.S. Haldane from using W_bar in his equation for genetic load:

L = (W_max - W_bar) / W_max

where W_max is the theorertical maximum of mean fitness. Haldane decided that mean fitness actually measures something, and that a population with higher mean fitness is, well, more fit. This goes contra to the paradigm of natural selection, in which fitness is measured for individuals not populations.

Kourennyi makes a valid point in his letter when he points out that evolutionary theory says nothing about the fitness of populations, but he slips a bit when he claims that cheaters affect the fitness of a population. The fitness of a population does not measure the health or vitality of a population; it simply standardizes an equation for calculating changes in allele frequencies.

A Few Words on Speciation

2005-12-19T22:16:00.000-05:00

John Wilkins has been writing about modes of speciation (who would've thunk it?), using Sergey Gavrilets's recent book, Fitness Landscapes and the Origin of Species, as a framework. I have not read the Gavrilets book, but I am familiar with a lot of the literature on speciation -- mostly that dealing with studies of the genetics of speciation in natural populations. Wilkins has been writing about how we define modes of speciation (allopatric, sympatric, chromosomal, etc), and I like how he has framed the issue. Rather than individual types of speciation, Wilkins shows how there is overlap between the different modes and certain modes tend to occur with other modes. Both posts are worth reading, and I'm hoping he keeps them coming.

While I don't study speciation, what I have read in the literature has gotten me thinking about allopatric and sympatric speciation. I prefer to define sympatry and allopatry based on gene flow rather than geographic range (note that these are not mutually exclusive, as gene flow depends on geographical isolation). In this framework two sympatric population are essentially one single population with complete migration between them (m=0.5). Conversely, two allopatric populations are reproductively isolated (either pre-zygotically or post-zygotically) such that m=0. If 0<m<0.5, the populations are parapatric.

In studying speciation in natural populations, we can sample speciating populations at different points in the process. For example, two populations that recently became geographically isolated give a snap-shot of the early stages of speciation. Two populations that are partially reproductively isolated (due to mediocre mate discrimination, incomplete post-zygotic isolation, etc.) show the intermediate stages of speciation. Finally, two populations that have nearly complete reproductive isolation due to genetic factors provide insights into the later stages of speciation. From studying species pairs at different stages, we can increase our understanding of the entire speciation process.

This brings me to the current paradigms regarding sympatric speciation. Ernst Mayr advocated (and most biologists seem to agree) that allopatric speciation (now defined by geography) is the norm and sympatric speciation is very rare. There are some examples of geographical sympatric speciation (the Rhagoletis system is the most accepted), but they are few and far between. Even the sympatric nature of the Rhagoletis system has been called into question -- traditionally by the argument that host shifts due not really constitute sympatric speciation, and more recently by molecular studies that show the genetic potential for speciation originated allopatrically (defined geographically). Unless we can observe the speciation process from beginning to end (I know, I'm sounding like a creationist) we have no way of knowing that speciation was entirely sympatric.

Biologists can only measure the current (and recent) gene flow between populations. It is difficult to impossible to determine whether two populations ever were geographically isolated at some point in the past. The recent work on Rhagoletis, as well as the best model we have for chromosomal speciation with gene flow suggests that even sympatric speciation requires geographic isolation (or some other reproductively isolation) to allow for genetic differentiation between the populations. When these populations come back into contact, reinforcement favors the evolution of pre-zygotic and post-zygotic isolating barriers due to decreased fitness of the hybrids. If this is the case, we need to redefine the dichotomy, moving away from sympatric and allopatric speciation. Instead, the two modes should be “entirely allopatric” and “allopatry with reinforcement”. This new framework provides two plausible modes of speciation (rather than the extremely unlikely entirely sympatric speciation), but the mechanisms of speciation would still differ between the two modes so the dichotomy is biologically meaningful.

My Own Personal Launching Pad

2005-12-19T15:03:00.000-05:00

Yesterday, before I got pissed off at FOX for airing Cuckoo Bananas' address rather than showing the Family Guy on time, I shoveled some snow in my backyard.

It turns out the hill is neither steep enough nor long enough to build up sufficient speed to get good air. In case you're wondering (and can't tell by the tracks in the snow), I'm a skier not one of those dopes who sit in the middle of a run taking up space.

The NIH’s Cancer Genomics Project

2005-12-19T10:34:00.000-05:00

In a move that you either view as ambitious (if you are a geneticists) or misguided (if you are a cell biologist) the NIH has unveiled a cancer genomics project. Nature reports the two perspectives:

“The project is a potentially huge undertaking that could take 10 years and cost US$1.5 billion. Its proponents say that tallying up all the genetic mutations in cancer cells may reveal new drug targets.

“But opponents argue that cancer biology is too poorly understood to make such a cataloguing approach viable and say that the money would be better spent on basic research into how cancer functions.”

The project will consist of the following steps:

Sample two or three types of tumors from multiple individuals (I’m guessing on the orders of hundreds or thousands of cancer patients).
Perform “high-throughput” analysis on the cells -- the Nature article indicates gene expression as one type of analysis, but does not describe any others. Maybe Orac knows of some other analyses.
Sequencing of about 2,000 genes from each of the tumors. How will the researchers choose these genes? I have no idea, and I don’t know if the heads of this project know.

A Washington Post article describes the different genetic causes of cancer, something the Nature article fails to do:

“Some cancers are caused by a mutation in a single gene that normally keeps a cell from making offspring. Others are caused by the mistaken duplication of a gene that promotes normal cell division, boosting its reproductive capacity to abnormal levels.

“In other cases, entire pieces of chromosomes -- long, gene-bearing strands of DNA inside cells -- break off and reattach to other chromosomes, inducing spurious and unregulated growth signals.

“Still other cancers result when rogue molecules attach themselves to genes whose job is to control cell division. Such “epigenetic” changes are invisible on standard tests that look for mutated genes because the genes themselves are healthy but are being manhandled by the other molecules.”

From the brief descriptions of the project I have been able to find, the proposed NIH research plan will only deal with mutations in single genes. Unless the “high-throughput” analyses that go unnamed consist of karyotyping or in situ probes for duplications, this study won’t even skim the surface of the genetics of cancer. I don’t think you can even do either of these in a high-throughput manner. The epigenetic effects may be picked up by the gene expression analysis, but it will be difficult to distinguish between mutations to regulatory regions (cis effects), mutations to transcription factors that control the expression of the gene (trans effects), and epigenetic effects.

Without more detail, it’s hard to judge the merits of this project. The research will definitely result in some worthwhile discoveries, but it may be wiser to spend the money on more detailed analyses. Just because “high-throughput” works for genome sequencing, doesn’t mean that Francis Collins needs to apply it to every study the National Human Genome Research Institute gets involved in.

Reason #342 why FOX sucks

2005-12-18T21:00:00.000-05:00

They cut into the Family Guy's time slot to show President Cuckoo Bananas' address to the nation about Iraq. I guess they didn't get the memo: Peter Griffin = good, George W. Bush = douchebag.

Fucking assholes.

Proponents of the theory are liars and bad scientists

2005-12-18T14:02:00.000-05:00

The New York Times has some more coverage on the Dover Panda Trial, this time consisting of a profile of Judge John E. Jones III. The article contains a paragraph regarding the potential scope of Judge Jones's decision:

"Legal experts said the big question was whether Judge Jones would rule narrowly or more broadly on the merits of teaching intelligent design as science. Proponents of the theory argue that living organisms are so complex that the best explanation is that a higher intelligence designed them."

Other than that, the article does not deal with the issues of the trial, instead focusing on Jones's political background, the attention of the national media, and his sharp wit. The author, Laurie Goodstein, does not bother to explain that intelligent design has no scientific merit, and the arguments by its proponents have been thoroughly disproven. Instead, she uses a description of intelligent design that we have grown so accustomed to reading: “Proponents of the theory . . . so complex . . . intelligently designed.” A simple Google search reveals how common this type of phrase is:

New York Times (18 Oct 2005): “Proponents of intelligent design, however, argue that living organisms are so complex that the best explanation is that a higher intelligence designed them.”
New York Times (4 Nov 2005): “The More center's lawyers put scientists on the witness stand who argued that intelligent design - the idea that living organisms are so complex that the best explanation is that a higher intelligence designed them - is a credible scientific theory and not religion because it never identifies God as the designer.”
New York Times (27 Sep 2005): “Intelligent design is the idea that living organisms are so complex that the best explanation is that some kind of higher intelligence designed them.”
MSNBC (8 Nov 2005): “Intelligent design holds that the universe is so complex that it must have been created by a higher power.”

Two of the New York Times articles were written by Goodstein (and the MSNBC article substitutes "universe" for "living organisms"), but it appears that this description has circulated throughout the journalistic circles. I don’t have much of a problem the phrasing (it’s intelligent design in a nutshell -- in fact, it’s all intelligent design has to offer), but it would be nice to see the following:

Proponents of intelligent design argue that living organisms are so complex that they must have been designed by a higher intelligence. They have presented no evidence for their claims, have not experimentally tested their hypothesis, and their arguments are widely rejected amongst biologists.

I don’t even need to read a description of evolutionary theory (it’s so complex that it would take a few paragraphs to describe, and the crappy writers at the Times would probably screw it up), as long as the description of intelligent design is accompanied by the qualifier that it’s absolute bullshit.

Detecting Natural Selection (Part 4)

2005-12-17T13:56:00.000-05:00

Phylogenetics and Relative Rates

This is the fifth of multiple postings I plan to write about detecting natural selection using molecular data (ie, DNA sequences). The first post contained a brief introduction and can be found here. The second post described the organization of the genome, and the third described the organization of genes. The fourth post described codon based models for detecting selection.

The simple codon based model for detecting natural selection that I described previously (d_N/d_S) involves comparing two homologous sequences. If we have three or more sequences, we can create a rooted phylogeny, and four or more sequences allow us to create an unrooted phylogeny. With the analysis of d_N and d_S we were not concerned with which lineage the substitutions occurred on. In our relative rate analysis we will be determining were in the tree (on which branch) the substitutions occurred.

I will not get into the detail regarding different algorithms for creating phylogenies, and I will assume that we already know the evolutionary relationship of the sequences we are comparing. If you are interested in learning more about how phylogenies are created, I would recommend starting with this book and following the literature citations therein. I will point out that the length of the branches represents the number of substitutions that have accumulated along a particular lineage. Phylogenies can be created with either DNA sequences or translated protein coding sequences (amino acid sequences) depending on if the sequences are closely related or not. (DNA sequences are preferred for closely related sequences because they evolve faster and accumulate more substitutions in a shorter period of time, while amino acid sequences are preferred for more distantly related sequence because they evolve slower.)

Recall from our codon based comparisons that we have, essentially, three different selective scenarios:

Neutral evolution - a sequence is evolving without the constraint or influence of natural selection
Purifying selection or selective constraint - natural selection is acting as a conservative force, restricting the evolution of a sequence
Positive selection - natural selection is driving the evolution of a sequence, causing it to evolve faster than the neutral expectation

Relative rate tests compare the selective constraint along two lineages of a phylogeny. Assuming all other factors are equal (ie, population size, mutation rate, gametogenesis, generation time), if the selective constraint along both lineages is equal, the branch going from sequence A should be of equal length to the branch leading to sequence B. If, however, the selective constraints differ, the branch lengths should be unequal.

If there are more substitutions along one lineage than the other, we must invoke some explanation for these differences. In some cases, differences in rates can be attributed to life history differences of the species from which the two sequences come. For example, mice have much shorter life spans than humans, and this has been used to explain differences in rates of evolution between the two lineages. Body size and metabolic rate can also affect rates of evolution, as can whether the sequence is from an X-chromosome or autosome -- autosomes are found equally in males and females, whereas X-chromosomes are disproportionately found in females, and male gametogenesis involves more cell divisions (more potential for mutation) than female gametogenesis.

We can control for the effects of life history on rate differences by selecting two genes from a single genome (ie, duplicate genes) or obtaining sequences from organisms with similar life histories. If we are interested in comparing sequences from two species with known life history differences, we can sample multiple sequences from each of those species (as well as our third species). Life history should affect all sequences equally, whereas selection should only affect a subset of the sequences.

If we observe differences in rates along two lineages after controlling for other variables, we conclude that the selective constraints along the two lineages differ. The difference can be due to increased purifying selection along the slowly evolving lineage (the shorter branch) or positive selection along the rapidly evolving lineage (the longer branch). Distinguishing between these two hypotheses requires more information (such as difference in synonymous and non-synonymous substitutions). Some of the other assays for natural selection that I will describe can also be used to discriminate between increased selective constraint and positive selection.

I am not sure if I will post another entry on comparative and phylogenetic analyses, or if I will move on to discussing nucleotide polymorphism in my next post. If you have any suggestions, or further questions, please post them in the comments.

Weekly Random Ten (16 December 2005)

2005-12-16T14:48:00.000-05:00

Odds and Ends Edition

Alright, so it's been a couple of weeks since the last evolgen Weekly Random Ten. I'm sorry. Really, I am. I know how much none of you look forward to reading this warn out staple of my humble blog. It's also been a while since I published my most recent entry in the Detecting Natural Selection series. I hope to have the next post (on phylogenetics and relative rates) up soon (once I write it). I promise. Really, I do.

As for the post I promised on William Harris's talk, well, that's not gonna happen. Maybe I'll post what I've got written (about half of it), but I can't motivate myself to write any more about that intellectually vacuous drivel like some people. The same goes for he who shall not be named (aka, John Davison . . . oops, I guess I named him), who now has his own blog -- which I refuse to visit or link to (you can find it yourself if you need to see it, just search "I know nothing about chromosomal rearrangements and evolution").

Winter's almost here, though, judging by the recent snow/ice storm, I'd say it's already here. Don't forget to support our troops in the War on Christmas. I'm gonna wear my Cross-Buster t-shirt along with a Santa cap (y'know, cause the juxtaposition is such irony, and irony is so cool) while listening to this week's evolgen Random Ten.

Blood, Sweat & Tears - I Love You More Than You'll Ever Know
Foghat - Slow Ride
Bouncing Souls - Say Anything
AFI - Advances in Modern Technology
Long Beach Dub Allstars - Grass Cloud
Tilt - Past the Point
Nena - 99 Luftballons
Rancid - Stand Your Ground
The Fraternity of Man - Don't Bogart Me
Stealers Wheel - Stuck in the Middle

The Competitive World of Gene Naming

2005-12-16T09:16:00.000-05:00

Many genes have names, most do not. Drosophila geneticists are among the most clever at naming genes. Historically, genes have been named by the phenotype of the first mutation in that gene. For example, the first Drosophila mutation discovered disrupted a pigmentation pathway and cause the fly's eyes to be white (as opposed to the wild-type red hue). Thomas Hunt Morgan's lab named this mutation white, and now the gene is also known as white.

The white gene is a particular bad example of clever naming, but it does illustrate the naming process. Some of the more fun names include fruitless (that I've blogged on before and used to be known as fruity), tinman (problems with heart development), and Scott of the Antarctic (which makes me think of this). Other research communities have different ways of naming genes. Yeast geneticists are among the least interesting (when it comes to naming genes), using a combination of three letters and a number. The mouse/rat community seems to have dry naming rules as well, but it's hard to tell. One of my all time favorite gene names pays homage to the second greatest video game character of all time (behind Mario, of course), Sonic the Hedgehog. Mutations in the Drosophila gene hedgehog (which affects segmentation patterning) causes the embryo to look like a balled up hedgehog. When the homologous gene was identified in zebrafish in 1993, it was named sonic hedgehog after the popular video game.

Whole genome sequencing has added an extra dimension to the naming game. One of the first steps after assembling a completed genome is the annotation. This requires identifying all of the protein coding genes, tRNAs, rRNAs, transposable elements, and any other class of sequences in the genome using gene finding algorithms and alignments with closely related known sequences (including other sequenced genomes). The annotation process, however, is drastically different than traditional gene naming. During annotation, genes are assigned unique identifiers (usually some sequence of letters and numbers) regardless if the gene was named using a classic mutation experiment. Genes that were never named via mutagenesis (or some other molecular analysis of function) only go by their boring annotation identifier, but previously characterized genes get to keep their old names as well.

That brings me to a sad piece of news reported in Nature:

"A cancer research institute has been threatened with legal action by the US branch of Japanese video-game franchise Pokemon, after one of its researchers borrowed the company's trademark to name an oncogene."

The authors of the paper in question use the name Pokemon as a clever abbreviation for the genes functional description, POK erythroid myeloid ontogenic. Around the time of publication the paper received a fair bit of press, and people began saying things like, "Pokemon causes cancer." Not surprisingly, that got the folks behind the TV-show/video-game in a tizzy. Pokemon may cause seizures (the TV show not the gene), but the show does not cause cancer (although aberrant expression of the gene is found in cancer cells).

Do Wikis Work?

2005-12-14T16:53:00.000-05:00

Nature has examined the efficacy of Wikipedia (actually, accuracy would be a better word). Compared to Encyclopedia Britannica, wikis fair quite well when it comes to science articles:

"The exercise revealed numerous errors in both encyclopaedias, but among 42 entries tested, the difference in accuracy was not particularly great: the average science entry in Wikipedia contained around four inaccuracies; Britannica, about three."

Wikipedia often gets a lot of bad press for the gross errors -- such as people editing their own entries with alterior motives or providing misinformation -- but the Nature study revealed four major errors from each encyclopedia in the 50 entries examined. Nature sent out unlabeled entries from both Britannica and Wikipedia to experts in fields relating to the entries; these entries included Australopithecus africanus, Cambrian explosion, Dolly, Kin selection, Ernst Mayr, Mutation, Punctuated equilibrium (these are the entries that would probably interest regular readers of this blog).

One major complaint about wikis is not the content, but the manner of presentation:

"Editors at Britannica would not discuss the findings, but say their own studies of Wikipedia have uncovered numerous flaws. 'We have nothing against Wikipedia,' says Tom Panelas, director of corporate communications at the company's headquarters in Chicago. 'But it is not the case that errors creep in on an occasional basis or that a couple of articles are poorly written. There are lots of articles in that condition. They need a good editor.'"

The article seems to suggest, however, that the wikis don't so much need editors, as more experts writing articles. While armchair scientists may have some knowledge about a particular field, the experts would be able to add an extra dimension that people outside of the research community lack. I can see the Wikipedia entries being more akin to informal reviews that are distilled for the general public.

Nature also has a short report on this story.

Tangled Bank #43

2005-12-14T12:21:00.000-05:00

Tangled Bank #43 is up -- yes, you should check out the linkage.

Can Intelligent Designers Inseminate Virgins?

2005-12-13T16:16:00.000-05:00

Hooray for Humanzee

2005-12-13T16:10:00.000-05:00

John Wilkins points us to the inspiration for King Kong -- a Russian scientist’s failed attempts to create a human-chimpanzee hybrid. The conversation over at Pharyngula shifted to obstacles of hybridization between humans and chimps. PZ Myers thinks that differences in gene regulation between hybrids would present a greater barrier to hybridization than genome rearrangements. I agree with him that rearrangements themselves would not pose a problem for hybridization -- many species, including humans, are polymorphic for rearrangements. Also, the difference in chromosome number (humans have 23 pairs, chimps have 24 pairs) is not all that important because it results from a fusion of two chromosomes along the human lineage; both species have equivalent amounts of genomic information, it’s just arranged slightly different.

The rearrangements may still be important if they harbor genes responsible for the reproductive isolation between the two species. This is well supported in Drosophila and has been suggested in apes, but not without some disagreement. The theory posits that inversions will prevent the transfer of reproductive isolating factors between speciating populations by suppressing recombination. The problem with applying this theory to humans and chimps is that the model assumes range overlap during speciation, such that rearrangements are necessary to prevent gene flow between the two species in regions of the genome containing hybrid incompatibility factors. From what I understand, an important event during hominid-chimp speciation was the emigration of hominids from rain forests to open grass lands meaning the speciation occurred allopatrically. Hence, we have no reason to believe that the genomic rearrangements differentiating the human and chimp genomes play an important role in the reproductive isolation of the two species.

Human-chimp hybrids and evolutionary intermediates have interested scientist and lay-people alike for quite a long time. One particularly famous case involves a predominantly bipedal chimp named Oliver who was often referred to as a Humanzee (for human-chimpanzee hybrid). Oliver had many behaviors that seemed more human than chimp, leading some people to believe he was either the product of a human-chimp hybridization event or some evolutionary missing link. It turns out, via a simple molecular assay, that Oliver was 100% chimpanzee, and his human-like behaviors were often exaggerated. Oliver represents a good piece of evidence for the role of developmental plasticity in anatomical evolution -- one could imagine that his upright stance could have influenced other members of his community, thereby changing the selective pressures on the morphology of the population.

Studying the genetics of speciation represents a major paradox: the study of genetics (from Mendel to Morgan to current research done today) requires the crossing of different individuals to determine how traits are inherited, but species boundaries prevent those requisite matings. Research on the genetics of speciation can be done using everyone’s favorite model system, Drosophila, by creating mutant flies that can mate across species boundaries. Surprisingly, mutations in single genes can break down those species boundaries, allowing for viable hybridization between D. melanogaster and its close relatives. Geneticists can create inter-specific hybrids using these mutant flies and study the effects of transcriptional regulatory elements on the differences in gene expression (something would obviously interest Dr. Myers). So far, a few speciation genes have been identified, but their protein products do not fall into a particular class -- they include transcription factors and a component of the nuclear pore complex.

It’s hard to refute the idea that transcriptional regulation is important in speciation, given both the analysis of expression differences between species and the identification of transcription factors that prevent hybridization. I guess I’m going to have to agree with the developmental biologist on this one -- the human-chimpanzee hybridization experiments probably failed due to regulatory differences (along with problems in sperm-egg recognition proteins). Also, God probably wouldn’t have wanted it to happen anyway.

Do These People Work at the Gap?

2005-12-09T16:38:00.000-05:00

Individuals who are red-green color blind cannot distinguish between the colors red and green (makes sense). One type of red-green color blindness (deuteranomaly) is due to a recessive mutation on the X-chromosome. Men are more likely to be red-green color blind because they only have one copy of the X-chromosome, whereas women can carry the mutant allele on one copy of the X-chromosome and still have normal color vision if they have a wild-type copy on their other X-chromosome.

A new study reveals a hidden benefit of red-green color blindness -- the ability to distinguish 15 shades of khaki.

"They identified 15 shades of khaki that fitted the bill, and tested their prediction by showing two sets of subjects - one with deuteranomaly and the other with normal vision - a series of cards carrying pairs of different khaki shades. It proved to be almost impossible for people with normal vision to tell the colours apart."

At first thought, one might imagine this mutation would be beneficial for men picking out slacks at their local department store, but it turns out that the recessive allele may have aided the color-blind males when hunting.

"Simmons hypothesizes that because deuteranomaly is quite common in human populations, the gene responsible may have once provided an evolutionary benefit. For example, it may have helped them spot potential food items in complicated environments such as grass or foliage, he suggests."

I find this hypothesis to be a bit of a stretch. A simple analysis of the frequency of the allele may reveal that it is maintained in mutation-selection equilibrium. For example, some people have suggested that the prevalence of cystic fibrosis is due to a beneficial quality of being heterozygous for a mutation that causes the disease, but it can be adequately explained by the mutation rate from the wild-type allele to the disease causing allele.

A final note on color-blindness and powerpoint presentations: always make figures in your presentations as black and white as possible. You never know when an audience member (especially an important one) cannot distinguish between red and green. You may end up discussing two trend-lines that some people won't be able to tell apart.

J'like dags?

2005-12-09T15:24:00.000-05:00

Afarensis reported some of the popular press surrounding the publication of the dog genome. One item from National Geographic's coverage seemed a bit odd:

"Scientists had previously found that about 5 percent of the human genome sequence appears in the mouse genome. The new study shows that 5 percent of the human genome is also shared with dogs."

This made absolutely no sense to me. It sounds like they are saying that there is 5% sequence identity between humans, mice, and dogs -- this is totally erroneous considering the following quote from the mouse genome publication:

"At the nucleotide level, approximately 40% of the human genome can be aligned to the mouse genome. These sequences seem to represent most of the orthologous sequences that remain in both lineages from the common ancestor, with the rest likely to have been deleted in one or both genomes."

From reading the Nature report of the genome sequence, however, I have discovered the true meaning of the five percent:

"A comparative analysis of the human, mouse and dog by Lindblad-Toh et al. showed that about 5% of the human genome is being maintained by natural selection - suggesting that it has some essential function. Almost all of this sequence is also present in the dog genome. Only 1-2% of the genomes encodes proteins, so there would seem to be an additional common set (about 3%) of functional elements in mammalian non-coding DNA. These common sequences may constitute, for example, regulatory elements, structural elements or RNA genes. Notably, such regions are found mostly within the 0.8 Gbp of ancestral sequence common to human, mouse and dog."

I have not read the actual article (I plan to, and if it's interesting I'll blog on it), but it appears that 5% of the genome is more conserved that expected based on neutral evolution. As they mention, genes are expected to evolve slower (be more conserved), but there is also a substantial suite of regulatory elements that are also under strong purifying selection.

Support NIH Funding

2005-12-08T18:59:00.000-05:00

The Genetics Society of America is encouraging its members to write to their US Representative. If you are currently doing research or have received support from the NIH, please write to your Representative.

We have a second chance to influence the fiscal year 2006 budget for NIH. Before leaving town for the Thanksgiving Day break, the House rejected the conference agreement reached on the Labor-HHS-Education appropriations bill for fiscal year 2006.

While a number of factors contributed to the defeat of this bill, certainly one of the main reasons was the bill's failure to fund critical health and education programs adequately. NIH's growth, for example, would be held to about $250 million (a 0.7% increase), the smallest increase in more than three decades.

The Senate responded by instructing its conferees to support the Senate recommended amount for NIH ($29.4 billion, a $1 billion increase [3.7% increase]). However, the House is resisting adding any more money for NIH.

Therefore, please urge your Representative to support the Senate passed recommendation of $29.4 billion by clicking here: http://capwiz.com/faseb/home/

The Greats of Evolutionary Genetics

2005-12-06T22:29:00.000-05:00

I often reference the classic minds of evolutionary genetics (Dobzhanksy, Wright, and others), but I tend to leave off one of the most important geneticist of them all, H.J. Muller. Thankfully, James Crow has published an short biography of Muller in Nature Reviews Genetics focusing on Muller's contribution to evolutionary biology.

"Although Hermann Joseph Muller is best remembered for his discovery that X-irradiation induces genetic mutations, for which he won the Nobel Prize, he made many influential contributions to evolutionary biology. Muller was the first to emphasize a gene-centred view of evolution, and he made both experimental and theoretical contributions to our understanding of speciation. He also reached insightful conclusions about how genes interact, how they are acted on by natural selection, and how their evolution is influenced by sexual reproduction and population structure. His influence on genetics and evolution was therefore substantial and wide ranging . . . In fact, Muller's interest in evolution pervaded his entire career."

Muller began his career in Thomas Hunt Morgan's lab at Columbia working with Sturtevant and Bridges. While Sturtevant is best known for constructing the first genetic map, Muller is best known for understand the physical nature of chromosomes. Muller received his Nobel prize for his work on X-irradiation and mutation, but he also made other discoveries regarding the homology of chromosomes. He showed that the chromosome arms in Drosophila have the same genes (are homologous) between multiple species. For this discovery, the chromosome arms are known as "Muller's Elements".

Some of Muller's other contributions to evolutionary genetics include:

The importance of duplicate genes (through examination of the Bar locus)
The importance of sexual reproduction in reducing genetic load (Muller's Ratchet)
A multi-locus model for the speciation via hybrid incompatibility factors (Dobzhansky-Muller incompatibilities)

I feel like I should also include some of the low-lights of Muller's career. He spent a lot of time bouncing around between academic institutions. He left the United States in 1932 (his communist beliefs conflicted with the current social environment) for Germany, only to see the rise of Hitler's Nazi party less than one year later. This led to a move to Russia, where research on evolutionary biology was stagnated by Lysenkoism. Eventually, he returned to America, but had difficulty finding a faculty position.

"Having been to Russia, he was branded as a communist, and having spoken out against Lysenko, he was branded as a fascist. With wry amusement, he once said that at least both could not be true."

Eventually, Muller was hired by Indiana University in 1945, and earned his Nobel prize in 1946. His work is some of the most important in both genetics and evolutionary biology. If you have access to the Nature publications, I suggest you read the entire article -- Crow tells both a human story and the story of a scientist.

What, US worry?

2005-12-06T07:24:00.000-05:00

This is more down Chris Mooney's alley, but still:

The Fatal Flaw

2005-12-04T21:28:00.000-05:00

It's that time of the year again, when the snow begins to fall, houses are outlined by white lights, and old white men don brightly colored sports coats. No, I'm not talking about Christmakwanzakah -- it's college football's bowl season! (Also known as "The Single Worst Way to Decide a National Champion".) This year, the Bowl Championship Series (BCS) lucked out and only two teams finished with undefeated records. If only it were always so easy.

In the previous two years, the BCS has seen three teams finish undefeated and only one team finish undefeated. In this current system (better than what existed prior to the BCS, worse than what we would have in an ideal world) a mixture of human voters and computer algorithms decide the top two teams in the nation (in addition to ranking the top 25 teams). These two teams play each other in early January for the right to be called the ~~ESPN~~/USA Today/Coaches Poll/BCS national champion, and get to keep this pretty crystal trophy:

In situations where there are more than two teams that can legitimately claim the right to play in this game, we have what can be lightly referred to as "controversy". This year, only Texas and USC finished the regular season with unblemished records, removing any doubt regarding who should play in the national championship game. This, however, does not mean that the BCS is devoid of controversy, as there are 3 other high payout bowl games involved. The participants in the four games (the national championship and the three other games) are determined as follows:

6 automatic invitations: The six conferences involved (the Big East, ACC, SEC, Big Ten, Big 12, PAC10) each get an automatic invitation for their conference champion.
Other automatic invitations: If a team from one of the BCS conferences does not win its conference, but finishes in the top four in the BCS standings, they get an automatic invitation to one of the BCS games. If a team from a non-BCS conference finishes in the top six in the BCS standings, they get an automatic invitation.
At large invitations: Finally, if there are any invitations remaining, any other team that finishes in the top twelve in the BCS standings can be invited to a BCS game.

This year, after the automatic invitations were handed out for conference champions, one non-BCS team (Notre Dame) finished sixth in the BCS standings, earning an automatic invitation. Additionally, a team from a BCS conference that did not win its conference (Ohio State) finished fourth in the standings and earned the final automatic bid. This means that there were no at large invitations available, much to the University of Oregon's dismay. You see, they finished fifth in the final rankings, but were not one of the eight teams chosen to play in a BCS game due to eight automatic invitations being handed out.

There isn't much Oregon can do about being left out, but is it possible for more than eight teams to qualify for BCS bowl games? Imagine the following scenario:

The top two teams in the BCS poll automatically qualify for the national championship, but one of the teams fails to win its conference (it has happened before) -- 2 bids
Another bid is given to the team that won the conference that one of the top two teams did not win, and four other bids are given to each of the other conference winners -- 5 bids
One other non-conference champion finishes in the top four (like Ohio State did this year), and a team from a non-BCS conference finishes in the top six (like Notre Dame this year, or Utah last season) -- 2 bids

That's nine bids for eight available positions (there are other possible combinations that I'll leave for the reader to figure out). Remember, being a conference champion says nothing about where you rank in the BCS poll (this year, the six conference champions finished ranked 1, 2, 3, 7, 10, and 22 in the final poll). Considering that all of the possible events needed to cause a total breakdown of the BCS have occurred at least once, this does not seem like it's too much of a stretch.

So, what can the BCS do to remedy this? Next year, there will be an extra game, which means two more teams will qualify (ten total). Is it possible for more than ten teams to automatically qualify for BCS games?

The six conference champions automatically qualify, but only one of those teams is ranked in the top six in the BCS rankings, and none are ranked in the top two -- 6 bids
Both teams ranked 1 and 2 fail to win their conference championship -- 2 bids
One of the following combinations: (a) 2 non-conference champions finish ranked 3 & 4, and at least one non-BCS team finishes ranked 5 or 6; (b) at least one non-conference champion finishes ranked 3 or 4, and 2 non-BCS teams finish ranked 5 & 6 -- at least 3 bids

Ok, so this is more of a stretch than the first scenario, but it's still theoretically possible. What's important is we have shown that there is a fatal flaw in the BCS without even invoking the problems of picking the national champion -- there may simply be more teams automatically qualifying for BCS games than there are spaces for those teams in the games.

Of course, picking only two teams to play for the national championship only works in seasons in which two teams have better records than all other teams, and this only happens when exactly two teams finish with undefeated records. Some people have suggested a "plus one" system, in which an extra game is played after the regular bowl season. This system would not work in seasons in which there are two obvious choices (for example, this year) because it seems absurd to play an extra game -- just let those top two teams play for the national championship.

The only remedy that would work in all scenarios is a simple playoff between the top teams in the nation. This could be a four team playoff with the top 4 teams in the BCS rankings, a 6 team playoff with the top six teams (the top two teams get a first round bye), or an 8 team playoff (picking teams just as they are done with the current system, only eliminating the fatal flaw somehow). Why don't they do this (there are playoffs in every other collegiate sport in the United States, including at the lower levels of college football)? Because the university presidents claim that the additional games due to a playoff would detract from the time the players should devote toward academics. Oh, the bitter-sweet taste of irony!

I apologize if you expected this post to contain anything relating to evolution or genetics. This was far to important to not post.

Genomics in the Post-Genomics Era

2005-12-03T10:23:00.000-05:00

Sahotra Sarkar points us to the new Post-Genomics blog, with an impressive list of contributors. I'm having a hard time pinning down the exact dates of the Pre-Genomics, Genomics, and Post-Genomics eras. Francis Collins and colleagues presented a "blueprint for the genomic era" in 2003. Nature, however, also published a jobs editorial entitled Bioinformatics in a post-genomics age in 1997. It seems illogical that the post-genomics age occurred prior to the genomics era.

So, does "post-genomics" really mean anything? In short, no. The longer answer is, well, not really, but kinda, if you look at it one way. Sort of. I see "post-genomics" as a synonym for "the genomics era". There are, in fact, only two eras. We have the time prior to whole genome sequences, or the pre-genomics era. In the last ten years, we have seen a dramatic increase in the amount of sequence data publicly available, including many whole genome sequences. With multiple genome sequences available, we are now in the (post-) genomics era. Call it whichever you prefer, just make sure you understand that there really isn't a difference between the post-genomics and genomics eras.

On Pedagogy and Cartography

2005-12-03T08:33:00.000-05:00

What does it mean to "Teach the Controversy"? In short, it means different things to different people. To an intelligent design creationist, it means presenting creationism as a valid alternative to evolutionary biology (descent with modification, natural selection, etc) to impressionable high school children. To a trained biologist, it means explaining creationist claims, then invalidating them with science. But does this approach work? Steve Verhey, an assistant professor of biology at Central Washington University, seems to think so. Verhey's paper can be found as a link from his webpage, where he has also made some other resources available. The Panda's Thumb also has an entry devoted to the Verhey article, which questions some of his statistical analysis.

I would be remiss to not mention that biology education is not the only curriculum getting the shaft in America's public schools. Lenny Flank points out:

"I think that the US education system *as a whole* is a mess, not just biology, and not even just science. Poll after poll shows that many Americans don't know what country the US won independence from, can't find the US on a world map, can't name the Vice President of the US, and think 'from each according to ability, to each according to need' comes from the US Constitution."

Of course, some of our children is learning (thank you Mr. President), as you can see by this map of the United States.

Species Sampling for Whole Genome Sequencing

2005-12-02T12:03:00.000-05:00

Now that we have entered the post-genomics era, with the genomes of most model organisms completely sequenced (as well as the human genome), it is up to genome centers, researchers, and funding agencies to decide which genomes to sequence next. These decisions are influenced by previous research done on the organism, size of the genome (in base pairs, not genes), biology of the species, and its evolutionary relationship to other species with a complete genome sequence. The process differs a bit between bacterial and eukaryotic species (and within eukaryotes, between animals, plants, and fungi -- and within the different animal groups: insects, vertebrates, etc) because of general differences in genome size, biology, and previous knowledge in these taxa, but many concerns are universal.

In the Drosophila community, for example, much consideration went into picking the second genome to sequence (after D. melanogaster, of course). D. pseudoobscura was chosen because it was thought that important non-coding sequences could be identified through comparisons with D. melanogaster. In turns out that the two non-coding sequences from these two species are too divergent to align homologous regions, so conserved non-coding sequences could not be identified. This was not entirely detrimental, as the comparisons of gene order between species revealed insights into the origin and evolution of genome rearrangements.

Currently, ten more Drosophila genomes are in the process of being sequenced and analyzed for publication. In choosing these genomes, the major players in Drosophila genomics decided to focus on developing annotation and analysis tools, studying tempos of evolution, and examining speciation. The third and fourth species to be sequenced (D. simulans and D. yakuba) are both close relatives of D. melanogaster (at least closer than D. pseudoobscura). Other species were chosen to get different amounts of divergence from D. melanogaster, from closely related species (D. erecta and D. ananassae) to more divergent species (D. willistoni, D. mojavensis, D. virilis, and D. grimshawi). All of these species represent some of the best studied for a particular amount of divergence from D. melanogaster. Furthermore, two other species (D. sechellia and D. persimilis) were chosen for studying the genetics of speciation because of their close relationship with other species getting their genome sequenced. The D. pseudoobscura - D. persimilis system is one of the best studied, dating back to work done by Dobzhanksy, but also including really cool stuff on behavior, genetics, and ecology getting done today. The whole genome sequences of these two species are already being put to use to study the genetics of speciation.

The species sampling strategy for Drosophila genomes will be tested during the genome analysis stage (currently underway). If it proves to be successful, it should serve as a model for other whole genome sequencing in other taxa. But what about other approaches? A paper by Fabio Pardiand Nick Goldman in PLoS Genetics (it’s free, so you have no excuse not to read it) presents a new approach toward species sampling in genomics. They begin with the assumption that, ultimately, sequencing projects would like to maximize the amount of divergence between species sampled in some taxonomic group. I question this assumption, as the Drosophila projects do not follow this strategy (they include an excess of species closely related to D. melanogaster), and the current sequencing in mammals does not either (too many primates). If, however, we look exclude primates from the mammalian sequencing projects, it does appear that the sequencing projects are attempting to maximize divergence.

Figure 1.

Phylogenetic Scopes and Divergence of Sets of Species

(A) Phylogenetic scope comprising hypothetical species A, B, C, D, and E. Numbers are branch lengths indicating evolutionary distances (not necessarily reflecting temporal distances). The subtree connecting species B, C, and E is shown in red and has divergence 1 + 3 + 1 + 5 + 2 + 4 = 16. Applying the greedy algorithm always produces maximally divergent extensions of the original set. For example, the subsets constructed starting with B—BE (divergence 11), BCE (16), BCDE (19)—have maximum divergence among those obtainable by adding one, two, and three additional species, respectively. The series AE (12), ACE (17), ACDE (20) is optimal among all possible subsets of two, three, and four species.

(B) Phylogenetic scope comprising placental mammals that have been or are being sequenced (in red) and candidates for future sequencing. If five groups choose the next five targets for sequencing using the greedy strategy described in the text, the following species (in blue) will be selected (in order): (1) tenrec, (2) hedgehog, (3) rock hyrax, (4) tree shrew, (5) dog-faced fruit bat (a megabat). Within the phylogenetic scope shown, this is guaranteed to be the choice of five species that maximises the total resulting divergence. These species have recently been announced amongst targets for future sequencing.

The paper asks, “How can we ensure that divergence is maximized in sampled genomes?” Well, it turns out that if each sequencing project was chosen independently so as to sequence the single most divergent genome, we would get the same result as if they were all chosen together to maximize all of the divergence between sampled species. Thus, the “greedy” algorithm (each project only looking out for its own self-interests) is just as successful as a more holistic approach. The groups that sequence particular genomes must make their choices open to the rest of the research community, as they influence future decisions, but we do not need to plan more than one step ahead. This comes as a surprise because greedy algorithms are not usually the best way to solve a computational problem.

The greedy algorithm can also be applied to projects such as the Drosophila genomes, in which maximizing divergence was not the ultimate goal. In cases where we would like to sequence genomes with different amounts of divergence from some model organism (ie, D. melanogaster) we must employ an incremental approach. This approach allows us to identify sequence conservation for different amounts of divergence. Important, but rapidly evolving sequences, can be identified using the closely related species, whereas more conserved sequences can be differentiated using more divergent species. Non-coding sequences, for example, evolve faster than protein-coding sequences, so conserved non-coding sequences can only be identified using close relatives. Amino acid (or protein) sequences evolve slower, and these would not differ much between close relatives, so we need more distant species to study these sequences.

Despite the formal proof that the greedy algorithm works for different sequencing strategies, I doubt we will see this type of selfish behavior from sequencing centers. If they do choose to sequence a genome for self-serving purposes, it will most likely be because a particular organism interests them, and not to maximize divergence or pick the next most divergent species. Altruistic results will probably come from consciously cooperative behavior.

Pardi F, Goldman N. 2005. Species choice for comparative genomics: being greedy works. PLoS Genet. 1: e71

Richards, S, Liu, Y, Bettencourt, BR., Hradecky, P, Letovsky, S, et al. 2005. Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution. Genome Res. 15: 1-18

First Walmart, now Target -- where am I allowed to shop?

2005-12-02T08:33:00.000-05:00

I've briefly mentioned my disdain for Walmart before. Now it turns out Target (the blue-state alternative to Walmart's red-state charm) is allowing their pharmacists to refuse to dispense the Plan B contraceptive if it conflicts with the pharmacist's religious beliefs. I won't get into why I find this objectionable, but suffice it to say, I do.

I have already decided to boycott Walmart unless I absolutely have no other choice (ie, if Walmart is the only place that carries a particular product). I have shopped at Target for a while now, and I find their products of a higher quality than those at Walmart, their stores cleaner, and the people that work there generally friendlier. If I include Target in my list of stores to boycott, I will add extra agony to the pain of shopping. You see, I live in a small town. Our choices of one-stop shopping includes a Walmart, a Super Walmart, a Sam's Club (the Walmart membership store), and a Target. Yes, that's 3 Walmart stores, one Target, and nothing else. No K-Mart. No Costco. No options.

I don't buy a lot of things (as evidenced by my rant against Black Friday), and when I do, I often shop online. The only regular shopping I do is at the grocery store and for other general crap. Target comes in handy when I want to buy the general crap -- if I need something for the kitchen or bathroom, I know I can find it at Target. If I exclude the only remaining acceptable one-stop store in my town, I don't know where I will buy all of that general crap. What the hell did people do before these mega-stores began taking over small towns?

Detecting Natural Selection (Part 3)

2005-12-01T16:58:00.000-05:00

Codon Based Models for Detecting Selection

This is the fourth of multiple postings I plan to write about detecting natural selection using molecular data (ie, DNA sequences). The first post contained a brief introduction and can be found here. The second post described the organization of the genome, and the third described the organization of genes.

As I mentioned in the previous post in this series, we can divide genes into protein coding sequence and non-coding sequence. Protein coding sequences are made up of codons (sets of three nucleotides) which encode amino acids. Because of the redundancy of genetic code (64 possible codons, but only 20 amino acids), many amino acids are encoded by multiple codons (see the codon table above). Nucleotide substitutions that do not change the amino acid encoded by a codon are said to be synonymous (or silent). Those that do change the amino acid are non-synonymous (some people refer to these as replacement substitutions).

Tests for natural selection often compare one set of nucleotides (or sites) which may be under selection to another set of nucleotides (or sites) that are probably not under selection. The sites that are not under selection are said to be evolving under neutral processes, and they act as a scientific control. The patterns of evolution at the sites that may be under selection (the experimental group) are then compared to the neutral sites. If both sets are evolving similarly, then we fail to reject neutrality at the second set of sites. Conversely, if the two types of sites are evolving at different rates, we reject neutrality.

If we assume that selection acts on the amino acid sequence (the protein encoded by the gene) then the synonymous substitutions should be selectively neutral. This is not necessarily true, and is a legitimate concern in some instances, but we will ignore it here. We can count the number of synonymous and non-synonymous substitutions in a gene if we have a copy from two different species (for example, human and mouse). To standardize for differences in the number of synonymous and non-synonymous sites (there are more than twice as many non-synonymous sites in a coding sequence because, for the most part, only the third codon position is redundant), we calculate the number of synonymous differences per synonymous sites (k_S or d_S) and the number of non-synonymous differences per non-synonymous sites (k_A or d_N). The two types of statistics (d_S and d_N versus k_S and k_A) differ in how synonymous and non-synonymous sites are calculated -- for this discussion, I will be using d_S and d_N.

Once we have calculated the fraction of synonymous (d_S) and non-synonymous (d_N) sites that differ between the two sequences, we can compare them. Each statistic is a proportion, so the possible values range from zero (no differences) to one (all sites are different). (An aside for anyone interested: Because two random nucleotide sequences are expected to match at 25% of their sites, values of d_S and d_N greater than 0.75 are theoretically unobtainable, and various corrections have been developed to calculate the actual number of substitutions for more diverged sequences.) Assuming that d_S is an adequate estimate of the neutral rate of molecular evolution we interpret the three different outcomes of comparisons between d_N and d_S thusly:

If d_N < d_S : Non-synonymous sites are evolving slower than synonymous sites. We interpret this to mean that the non-synonymous sites are under selective constraint (or purifying selection) because they are evolving at a rate slower than the neutral expectation. This is the case for most genes when comparisons are made between any two species. This means that most amino acid substitutions are deleterious.

If d_N = d_S : Non-synonymous and synonymous sites are evolving at equal rates. Hence, non-synonymous substitutions are neutral.

If d_N > d_S : Non-synonymous sites are evolving faster than synonymous sites. This is evidence for positive selection because we assume that natural selection is acting on the amino acid sequence of the protein.

The relationship between d_N and d_S is often summarized by the ratio of the two statistics (d_N/d_S). If d_S>d_N then 1>d_N/d_S; if d_N=d_S then d_N/d_S=1; if d_N>d_S then d_N/d_S>1.

There are some obvious limitations (and some more subtle ones) to using d_N and d_S to identify genes under positive selection. As I mentioned earlier, d_S may not be an adequate estimate of neutral evolution. Furthermore, when only one (or very few) amino acids are under positive selection, these statistics are not very sensitive to that selection. If synonymous substitutions accumulate, in general, at a faster rate than non-synonymous substitutions, the one (or few) amino acid substitution that occurs due to positive selection will not influence d_N enough to cause it to be significantly greater than d_S. One way to get around this problem is to perform a sliding window analysis (examine subsets of the coding sequence, say 30 codons at a time) to detect regions of a gene that have a signature of positive selection.

Despite its limitations, this codon based approach for detecting selection is widely used and provides the basis for other methods of detecting selection. Next time we will discuss phylogenetics and relative rates.

On Blogging and Site Statistics

2005-12-01T07:30:00.000-05:00

I just added Site Meter to my site (I had previously used StatCounter, and still discretely do). This was inspired by the "Where do your visitors come from" meme that has been circulating. Only Site Meter allows you to produce that nifty pie chart with a country-by-country breakdown.

That got me to thinking about visitor stats and how people read blogs. A lot folks (myself included) view blogs through their rss feeds using some sort of news reader (I use the online service Bloglines). I have chosen to make my entire entries available through the evolgen feed, whereas other people only supply a summary (or short excerpt).

If the entire entry is available in my news reader, I hardly ever visit many of the blogs I read regularly. The exception being when I would like to leave a comment, if something does not display correctly in the news reader, or if I plan to link to an entry from another blog. If a site only provides a summary in their feed, however, I find myself visiting that site more often simply because it's required if I would like to read the entire article. For these sites, I usually only read the summaries unless an entry piques my interest enough to cause me to visit the website and read the entire article.

In summary, if you provide a complete entry in your site feed, I will read more of your writing, but I will not visit your website very often. If you only provide a summary, I will not read as many of your blog entries, but I will visit your site more often. Do my readers agree with me on this? Also, it seems that a good way to inflate your site statistics is to only make summaries available through your feed so that you also get visits from the readers using rss feeds.

Detecting Natural Selection (Part 2)

2005-11-29T21:28:00.000-05:00

The Organization of the Genes

This is the third of multiple postings I plan to write about detecting natural selection using molecular data (ie, DNA sequences). The first posting contained a brief introduction and can be found here. The second post described the organization of the genome.

In the last entry I mentioned that the term gene is often used interchangeably with protein coding sequence. In this entry, I will describe the structure of protein coding genes. Only a portion of the gene contains protein coding sequences. We will divide the gene into multiple parts: exons, introns, upstream sequence (or 5’ flanking regions), and downstream sequence (3’ flanking regions). The exons contain the protein coding sequence, and they are separated by introns. The introns and exons are transcribed into RNA, the introns are then spliced out to make messenger RNA (mRNA), and then the mRNA (coding sequence) is translated into a protein.

(Note: The majority of life on earth is prokaryotic, and prokaryotic genes do not contain introns.)

The region upstream of the gene usually contains non-coding sequences that control when and how the coding sequences are transcribed into mRNA (the introns and downstream regions may also contain transcriptional regulatory regions). For more on the regulation of transcription check out this site. For the rest of this discussion, we will refer to two types of sequences: non-coding (introns and upstream and downstream regions) and protein coding.

The protein coding sequence of a gene is made up of sets of three nucleotides called codons. When the mRNA transcribed from a gene is translated into a protein, each codon encodes a single amino acid. Just like nucleotides are the building blocks of DNA, amino acids are the building blocks of proteins. There are 64 different 3 nucleotide combinations (4 different nucleotides in combinations of 3, or 4^{^3} = 64), but there are only 20 amino acids. That means that some amino acids are encoded by multiple codons. We refer to this as the redundancy of the genetic code.

The U’s in this figure are the RNA equivalent of the T’s in DNA.

The three nucleotides in a codon can each be referred to by their position in the codon: first, second, and third. Because of the redundancy of the genetic code, some codons encode the same amino acid as other codons. The codons that encode the same amino acid tend to have the same first and second nucleotide, but differ at the third codon position. For this reason, many mutations of the third codon position do not lead to a change in the amino acid encoded by the codon.

Mutations that do not lead to a change in the amino acid encoded by a codon are known as synonymous. Conversely, those that lead to a change in amino acid are called non-synonymous. Next time we will discuss how we can compare synonymous and non-synonymous differences between two coding sequences to infer natural selection.

Trudeau on Dilbert

2005-11-29T10:03:00.000-05:00

PZ Myers (of Pharyngula) and Scott Adams (creator of Dilbert) had a little disagreement over Adams's credentials to evaluate the biological theory of evolution. I side with PZ on this one -- he is, after all, a trained biologist.

Today, I came across this interview (pdf) with Doonesbury creator Garry Trudeau, in which he discusses the relevancy of his comic, and political cartooning in general, after 35 years of Doonesbury. He talks about satirists finding other outlets (SNL, The Daily Show, Letterman), but also explains his influence in bringing attention to the dialog in cartooning despite mediocre drawing. On this topic, he says:

"[T]he best strip of the last decade is 'Dilbert,' and it sure isn't because of the drawing."

I would say The Boondocks (the strip, not the crappy show on Cartoon Network) and Non-Sequitur have better writing and better drawing than Dilbert. Plus, Non-Sequitur rips on the pseudo-science that Scott Adams is happy to endorse in clever ways that Adams can only aspire to.

My Favorite Obscure Movie

2005-11-28T14:34:00.000-05:00

Tony at milkriverblog wants to create a list of bloggers' favorite obscure movies. I was hesitant to get involved because I couldn't think of any. Honestly, I don't really know what my favorite movies are. Then, this post by Sean at Cosmic Variance got me thinking about Terry Gilliam films. Sean watched Brazil recently, which is a good, somewhat obscure Gilliam film -- I like all Gilliam films because of his fearlessness and ability to take risks, even if they end in catastrophe.

So, Tony, I'm going to (belatedly) answer your call for obscure films, limiting myself to only things Gilliam related. I have not chosen a Terry Gilliam film (as they are not very obscure), but rather a film about Terry Gilliam trying to make a film: Lost in La Mancha. This film details the failed attempts of Gilliam and his crew to make The Man Who Killed Don Quixote. If you ever doubted Murphy's Law, this film will make you reconsider your doubts. Basically, everything that can go wrong does.

I would recommend Lost in La Mancha for any Gilliam fan, but I assume that they have all seen it by now. So, I recommend it to anyone who enjoyed Twelve Monkeys, The Adventures of Baron Munchausen (my favorite Gilliam film), Fear and Loathing in Los Vegas, or Time Bandits. It's also a great film for anyone who wants to learn about how movies get made (or not made, for that matter).

Test Your Scientific Literacy

2005-11-28T08:25:00.000-05:00

Just to prove that I am qualified to write about the things I write about, I give you this:

You Passed 8th Grade Science

Congratulations, you got 8/8 correct!

Could You Pass 8th Grade Science?

(Via Living the Scientific Life.)

Weekly Random Ten (27 November 2005)

2005-11-27T16:50:00.000-05:00

Not So Random Edition

If you came here looking for science, this post will be a disappointment. Sorry. Instead, I'll be talking about something I know very little about: music. It's kind of appropriate given that this is merely an introduction to a (not so) random collection of 10 songs. My taste in music is so bad, I have been told by multiple roommates to stop playing whatever crap I was listening to.

In the spirit of bad taste, I took another one of those stupid online quizzes, and found out which fucked up genius composer I am.

Joe Strummer... you've been through the cleansing
fire of punk, only to pick up a few venereal
diseases along the way. You're more of an
optimist when it comes to fucked-up genius.
But you can write wicked-deadly riffs and lyrics.

I thought, "That's cool -- I really like the Clash and the Mescaleros," and it got me to thinking about a documentary that I caught on IFC a short while back, Punk: Attitude. The film is an excellent introduction to early punk from New York City and London, but it falls a bit short when it comes to some of the more recent bands -- and by recent I mean post 1980.

The movie begins with the major influences of early punk: MC5, the Stooges, the New York Dolls from the US, Bowie and Mott the Hoople in the UK. There are other influences (including bands I can't think of off the top of my head and early rock n' roll like Little Richard), but I'm not going to spend all of my time listing them. The film also treats the early days of punk in New York well, showing footage of the Ramones, Richard Hell, the Dictators, and the other CBGBs regulars and interviewing some of the major players in that scene. Of course, the film also deals with the London 1977 scene, including interviews with Paul Simonon, Mick Jones, Poly Styrene, the Slits, Chrissie Hynde, etc.

In all, it's a fun movie for any interested in the history of rock n' roll (especially if you like punk). The old footage of concerts is great, and the folks telling the stories were the machines behind the revolution. The problem comes as the story shifts from the New York and London scene to the bands that were influenced by that music. The New Wave, No Wave, and Synthpop music that followed are briefly mentioned, as are the hardcore bands (they spend some time talking about Agnostic Front, Bad Brains, Black Flag, etc). But almost nothing is said about the California scene -- after a brief mention of Sonic Youth, Fugazi and some other in between bands, the film suddenly jumps to the early 1990s claiming, "Punk disappeared in the 1980s, only to reemerge in Seattle with Nirvana."

The new so-called punk bands (Blink 182, Sum 41) and other rock bands (for some reason, Limp Bizkit gets a fair bit of time in the film -- quite odd), were greatly influenced bands from the 1980s. The music from Los Angeles (Bad Religion, NOFX, Descendents) and the Bay Area (Operation Ivy and the other Gilman Street bands) are the inspiration behind a lot of the stuff that gets called punk today. It's as if the film-makers were trying to fit the film into a neat little 90 minute package, and cut 1985-90 to make it work. Making a documentary on punk and not including Epitaph or Lookout records may not be grounds for exportation from the punk nation, but it's somewhat odd. Also, they briefly mention the dub and reggae that was spun at the London clubs in between sets, but don't really deal with the ska/punk fusion that happened as a result or the two-tone bands that were probably influenced by it (Specials, Madness, etc).

Here it is, a not so random ten consisting of some of my favorite punk songs:

Buzzcocks - Ever Fallen in Love (With Someone You Shouldn't Have Fallen in Love With)?
The Clash - (White Man) in Hammersmith Palais
MC5 - Teenage Lust
Richard Hell and the Voidoids - Blank Generation
Bad Religion - You Are (The Government)
Rancid - Lady Liberty
Operation Ivy - Sound System
Social Distortion - Ball and Chain
Descendents - Jean is Dead
NOFX - Liza and Louise

Quote of the Day

2005-11-26T23:02:00.000-05:00

"If intelligent design really works, then why is my brother so ugly?"
Sam Kwasman, 54, actor, former voice of Donald Duck, Los Angeles

From the New York Times.

Thanksgiving Science Post

2005-11-25T23:25:00.000-05:00

A common rumor posits that tryptophan in turkey makes you sleepy after eating your Thanksgiving feast. Afarensis explains why this is erroneous.

Anyone who has taken an introductory genetics course is familiar with the tryptophan operon. This (along with the lac operon) is a classic model of transcriptional/translational regulation in prokaryotes. Operons are the combination of regulatory sequences and coding sequences that allow for expression of genes only when the enzymes encoded by those genes are needed. Otherwise, the genes are not transcribed -- this saves the cell energy because it does not need to create proteins when they are not needed. Transcription and translation are coupled in prokaryotes, so we can essentially use the terms interchangeably.

But what is tryptophan? It is one of the twenty amino acids encoded by the genetic code. It is the largest of the amino acids, and is encoded by a single codon (UGG). Being large means it is expensive to produce, so bacteria regulate its production using an operon, only expressing gene when quantities in the cell are low. Tryptophan is also a precursor for the neurotransmitter serotonin which is important in chemical in mood disorders.

Buy Nothing Day

2005-11-25T08:18:00.000-05:00

Traditionally, the day after Thanksgiving in the United States has been known as Black Friday. This marks the first day of the holiday/Christmas shopping season. Retailers offer amazing deals on their products to entice consumers into their stores.

Today (Friday, Nov 25) is also Buy Nothing Day in the United States and Canada, a sort of silent protest against this day of rampant consumerism. I only bring this up because at Thanksgiving dinner yesterday some of my friends were talking about going to Walmart at 5am today to get the best deals. This bothers me on two levels: it gives in to the consumer mentality and it supports a company notorious for its mistreatment of employees.

Happy Buy Nothing Day!

Buy Nothing Day is tomorrow (Saturday, Nov 26) in the U.K.

I'm Dreaming of . . .

2005-11-24T09:52:00.000-05:00

. . . a White Thanksgiving!!

Guess what I was greeted to upon looking out my window this morning.

This is our second snow of the year. We got some in October that melted when it warmed up again. This really throws a wrench in my plans to go for a morning bike ride before gorging myself on Turkey.

Detecting Natural Selection (Part 1)

2005-11-23T10:01:00.000-05:00

The Organization of the Genome

This is the second of multiple postings I plan to write about detecting natural selection using molecular data (ie, DNA sequences). The first posting contained a brief introduction and can be found here.

Before we can discuss how DNA sequences are used to identify evidence of natural selection, we must have an understanding of how the genome is organized. The genetic material that can be found in each and every one of your cells – and inside every cell in every living organism – is made up of two sugar-phosphate backbones connected by nitrogenous bases. The two strands are wrapped around each other in what is known as a double helix. The nitrogenous bases come in four flavors: adenine (A), guanine (G), thymine (T), and cytosine (C). The nitrogenous base along with the sugar and phosphate is known as a nucleotide. In the double helix, nucleotides pair – A is always paired with T, and G is always paired with C.

One molecule of DNA goes on for millions of nucleotides, and is known as a chromosome. Along with the DNA, chromosomes also have proteins bound to them that help them wrap up into neat little packages. Humans have 46 chromosomes in everyone one of their cells. Each chromosome has a mate, or homolog, that contains nearly all of the same information, so we divide 46 chromosomes into 23 pairs. For each of the 23 pairs, one copy comes from your mother and one from your father. One of these pairs is a special set known as sex chromosomes (ie, X and Y). Females have two copies of the X chromosome (one from their mother and one from their father), whereas males have one X (from mom) and one Y (from dad). The National Center for Biotechnology Information has created a nifty genome browser that lets you explore the contents of each chromosome.

Some of the sequences of nucleotides contain information that leads to the production of proteins. These proteins carry out essential functions within the cell (such as the production of more proteins), allow for communication between cells, and regulate cell division, among the many other tasks they perform. The sequences containing the information to a produce a protein are known as coding sequences. (Note: some people refer to them as genes, but genes may also include sequences that encode RNAs that are never translated into proteins.) Each chromosome contains hundreds of coding sequences interspersed throughout the length of the DNA molecule. In between these coding sequences are non-coding sequences of nucleotides. These non-coding sequences may contain information that determines when and how the coding sequences are translated into proteins.

Here’s a little drawing showing two coding sequences separated by a non-coding sequence.

That’s it for now. Next time we’ll talk about the organization of coding sequences and their regulatory regions. I promise we’ll be discussing natural selection soon.

Weekly Random Ten (22 November 2005)

2005-11-22T10:59:00.000-05:00

No, this is not a "Special Turkey Day Edition" Edition

I'm sitting here in front of my computer, frustrated by my lack of programming skillz. I'm trying to write a very simple simulation to determine the statistical power of an experiment I performed. Every time I send a variable to a function that does binomial sampling, the variable gets altered. I'm not sending a pointer to the value; I'm sending the actual value. This is really pissing me off. I'm going to move the function into the body of the program and see what happens.

Anyway, that's how my week's been going. Thanksgiving's coming up, and I need to get these simulations done and analyzed, so I can write up the manuscript and submit it for review. I'm hoping to get this all done by the end of the semester, so I can focus my energies on some other analysis next year. We'll see how that goes.

Happy Turkey Day to all my American readers. To all my international readers, have a nice full week of work! I'll be taking some time off to gorge myself on food and watch some football, but nothing can match the excitement of last weekend. Reggie Bush is the second coming (of Gale Sayers), Fresno State is the best two loss team in the nation (yes, better than Notre Dame and Ohio State), and Oregon deserves to go to a BCS bowl game more than any other one loss team (their only loss cam to USC). I guess I just revealed my west-coast bias.

Time to get myself geared up for a tryptophan induced coma -- here's this week's evolgen Random Ten:

Inspector 7 - Sleeping With the Enemy
NOFX - Please Stop Fucking My Mom
Blondie - Maria
Anti-Flag - Die 4 Your Government
Bombshell Rocks - 21st Century Riot
U.S. Bombs - Jaks
88 Fingers Louie - Go Away
Eric Clapton - Cocaine
Mike Ness - I'm in Love With My Car
Tiger Army - Twenty Flight Rock

Detecting Natural Selection (Introduction)

2005-11-20T17:40:00.000-05:00

Introduction

This is the first of multiple postings I plan to write about detecting natural selection using molecular data (ie, DNA sequences). A lot of news releases in the popular press recently have dealt with genes under selection in humans. Most people probably don't understand what it means for a gene to be under selection and how researchers detect selection; I often throw around terms like “signature of selection”. These posts will explain some of the basic concepts in molecular evolution and the theory behind how selection is detected. They will be geared toward a scientifically literate reader, and I will do my best to explain the basics of molecular biology and genetics before getting into the nitty gritty. If you can read and understand PZ Myers, you should be in good shape. If John Hawks or Gene Expression are more your taste, this information will probably be old hat.

Throughout these posts, I will address the following:

The organization of the genome
Simple comparative methods for detecting selection
More complex comparative methods
Nucleotide variation in populations
Non-neutral patterns of sequence polymorphism

This is by no means a table of contents, as I have yet to write any of these entries. This will be a sort of dynamic primer of molecular evolution – the next topic will be determined by previous postings.

Check back soon for the first post in this series: “The Organization of the Genome”.

More Great Fake News

2005-11-17T15:30:00.000-05:00

I lamented earlier this week that the fake news does a better job of covering current events than the real news. Here is another example, this time from Sports Pickle:

A major milestone occurred today in the years-old debate over evolution and creation, when a leading creationist admitted he could be convinced that Vikings head coach Mike Tice is descended from apes.
Speaking this morning at a symposium on intelligent design at Princeton, Ken Hammond, who heads the well-known Creation Research Institute, stated that it would not surprise him if Tice's lineage could be traced to apes -- a statement that turns the evolution debate on its ear and likely threatens Hammond's standing among creation advocates.

I think they mean Ken Ham, who heads Answers in Genesis, not the Creation Research Institute or the Institute for Creation Research (or the Judean People's Front, for that matter). Maybe they were just watching their asses and didn't want to get sued.

This is especially funny considering the recent goings on surrounding Tice's team, the Minnesota Vikings. You see, some players chartered a couple of boats for a bye week cruise around Lake Minnetonka. The lake itself conjures up images of Purple Rain and Charlie Murphy, but the descriptions of the boat ride (cut short due to improper activity) makes Girls Gone Wild seem tame:

"They were out for a bit, and then the crew was serving drinks and hors d'oeuvres and stuff. I think the first thing they noticed was some of the women that were on board seemed to be either changing clothes or undressing. And then they went into a galley, and there were three of them in the nude that were changing clothes. That was followed by them coming out and some of them doing lap dances.... That's where it started, and then it just progressed to just bizarre."

I'll let you find the details elsewhere (I'm gonna try to keep this site R-rated, and avoid graphic NC-17 stuff). Anyway, Mike Tice is the coach of this team of sexual misfits, who may be charged with violating the Mann Act (transporting a person across state lines for sexual purposes) among other things. Tice, whom I regard as a stellar example of cronyism that causes some sports team to wallow in mediocrity, does look a little bit apish:

To provide support for his hypothesis that Tice descended from apes, "Hammond" presented the following during his talk:

One 20-minute montage of Tice's grunting speech patterns -- taken from his post-game press conferences -- were interspersed with monkey noises and left even the most skeptical viewer convinced that current day apes are more evolved than the Vikings coach. But perhaps the most damning evidence was the never-before-seen clip of Tice hurling his feces at former Minnesota receiver Randy Moss. Hammond then concluded his presentation by revealing that the average ape's IQ is 30-percent higher than Tice's.

I'll let them slip with "more evolved" crap, but the image of Tice hurling feces at Randy Moss is even better than Tice tearing a knee ligament while coaching. It would make a great two person Halloween costume: one person dresses up in a gorilla suit and another person wears this mask. Throw in a little novelty fake poo, and you've got the second best Minnesota Vikings themed costume ever.

So, what did we learn today:

It's fun to make fun of creationists.
It's fun to make fun of sexually adventurous football players.
It's fun to make fun of incompetent football coaches.
Minnesota is both the home of the purifying waters of Lake Minnetonka and science blogger PZ Myers.

Weekly Random Ten (17 November 2005)

2005-11-17T12:45:00.000-05:00

Science Against Evolution Edition

A friend of mine sent me a link to this site -- the official site of Science Against Evolution. I haven't toured the whole place yet, but it seems like an amalgamation of misinformation and common creationist canards.

Science Against Evolution is a California Public Benefit Corporation whose objective is to make the general public aware that the theory of evolution is not consistent with physical evidence and is no longer a respectable theory describing the origin of life.

Ha! Public benefit!? Ask the folks in Dover about the public benefit of violating the establishment clause. Guess what? The theory of evolution does not describe the origin of life, never did describe the origin of life, never will describe the origin of life, and never intends to describe the origin of life. The theory of evolution deals with changes in life on earth since the origin of life -- as Darwin so famously put it, "the origin of species".

They even have an entire page dedicated to "The Failure of Genetics" written in 1998 dealing with this review from Science. If you don't have access, this short review deals with how long external branches and short internal branches lead to incorrect phylogenies when using 18s RNA to determine the relationships of all animals. I'm not as committed to debunking individual creationist lies as some people, and boy is this page loaded with them, but I'll point out a few things.

The article then discusses a figure that shows that mollusks are more closely related to deuterostomes than arthropods when the creatures being compared are a scallop (a mollosk), a sea urchin (a deuterostome), and a brine shrimp (an arthropod). That isn't too surprising. Intuitively, a scallop seems more like a sea urchin than a shrimp, and the 82% correlation between the scallop and sea urchin shown on their diagram isn't surprising.

But when a tarantula is used as the representative of the arthropod, there is a 92% correlation between the scallop and the tarantula. It doesn't seem reasonable that a scallop should be more closely related to a harry [sic], land-dwelling spider than to a sea urchin.

It took me a while to figure out what they mean by "correlation". It turns out that the review has a figure showing bootstrap support of the nodes. Bootstrap values are calculated by randomly sampling the data (with replacement) to come up with a new data set and seeing if the results based on that new data set is consistent with those based on the original data. If you repeat this process multiple times and keep track of how many runs are consistent, you can get the bootstrap support for your data. This has nothing to do with correlation.

And the reason for doing molecular systematics is to overcome our subjective interpretation of phenotypic characters. It doesn't matter what something looks like upon first glance, because convergent evolution can lead to similar appearances despite different origins. You really need to take a much closer look to determine if the characters are homologous. This is so obvious my students look at me like I'm a moron when I tell them it in introductory biology.

If we ignore the author's absolute ignorance regarding simple statistical methods, we can focus on the total misinterpretation of the Science review.

Since the authors are evolutionists, it never occurs to them that the data doesn't agree with the assumed evolutionary relationship because the theory of evolution is wrong. They fall back to the old "evolution happened so fast we must have missed it" argument. They assume a "rapid divergence of most of the animal phyla" that caused not only missing link fossils, but also missing link RNA sequences.

The assumed evolutionary relationship is based on evidence -- assumptions made in scientific models tend to be based on previous studies. The inconsistencies in the trees can be attributed to a describable phenomenon: long branch attraction. If multiple taxa diverge in a short amount of evolutionary time, reassembling the order of divergence will be extremely difficult. This problem can be overcome with better taxanomic sampling. For example, if you add some intermediate relatives for each of the taxa (ie, chordates for the echinoderms), you can remedy the problem of convergent evolution in the rRNA sequences.

Another problem with rRNA is that there is epistatic selection operating to maintain the secondary structure of the molecule so the sights are not independent. To overcome this problem, you can construct trees with amino acid sequences. Ok, I'm sick of this shit . . .

Creationists suck! Here's this week's evolgen Random Ten:

Tiger Army - Outlaw Heart
Jimmy Cliff - Sitting in Limbo
No Use For A Name - On the Outside
Me First and the Gimme Gimmes - It's Raining on Prom Night
Teen Idols - Lovely Day
311 - What Was I Thinking
Mad Caddies - Booze Cruise
The Von Bondies - Poison Ivy
Redman - I'll Bee Dat!
Hot Hot Heat - Ladies and Gentleman

A Barrel of Monkeys

2005-11-15T11:22:00.000-05:00

If you don't read The Swift Report, you really should. Here's the headline to a recent article:

Student Suspended Over Evolution Slur
A seventh grade student at a south central Kansas junior high school has been suspended after implying that a classmate was descended from monkeys. School officials say that the student's two-week suspension was merited by the seriousness of the offense.

Classmates say student is member of an outlaw group called the "Biology Club"

The "Biology Club" is known to "typically keep to themselves", be "adherents of the notorious British naturalist Charles Darwin", "wear a lot of black and eat at their own table in the cafeteria." The student was found in possession of the following incriminating drawing:

Liberty Junior High School principal Marty Hamlin says that officials felt that they had no choice but to make an example of DuFresne. "Saying someone is descended from monkeys is about the worst thing you can say about that person. It's as bad as saying that someone's mother is a prostitute, or telling someone that they're adopted when they're not."

I love how the school is called Liberty Junior High, as if it's named after Liberty University, the bastion of science known for hosting the Mega Creation Conference.

As if this isn't enough, check out this article:

God Denies Links to Pat Robertson
God denied having any links to conservative Christian broadcaster Pat Robertson yesterday after He received reports that Mr. Robertson told residents of Dover, P.A., that they had rejected God by voting their school board out of office for supporting "intelligent design" and warned them of His wrath. Sources close to the Higher Being say that He is "tired" of Mr. Robertson and wants him to stop using His name.
God considering filing "cease and desist" letter

Why is it that the fake news seems to cover current events so much better than the real news?

Browser Switch

2005-11-13T22:53:00.000-05:00

I just switched from Netscape 8 to Firefox. I was running Netscape 8 because I liked how it let me view pages using either Firefox or IE, and it has a lot of good features built it (password management, pop up blocking, tabbed browsing, etc). The problem was, it took way too long to load and it kept crashing. I made the switch to Firefox hoping to find the same features (minus the ability to run IE), but I am now going through the process of installing the extensions that give me those features. I have already installed Tab Mixed Plus and JavaScript console. If you use Tab Mixed Plus, how long did it take you to figure out how to configure it properly? Are there any other extensions that are must haves?

As a reward for helping me out, check out this article in press from PNAS:

An index to quantify an individual's scientific research output
J.E. Hirsch
I propose the index h, defined asthe number of papers with citation number h, as a useful indexto characterize the scientific output of a researcher.

Yes, that's the entire abstract. Hat tip to Richard Gayle. I can't downloaded the PDF from home because my university's library gateway is currently down. If it's interesting, I may comment on it tomorrow when I hook in to the university network.

I need to get back to work shortening a grant proposal to the maximum page length (this has been a procrastination post). I'm caught in a Catch-22 between explaining everything for someone not familiar with bioinformatics and molecular population genetics, not lingering on unnecessary details, and providing enough information for someone who is familiar with the literature in these fields to make an informed evaluation. The entire thing is written, and now I'm selectively pruning.

Housekeeping

2005-11-12T19:46:00.000-05:00

You want me update your site?

For those of you that visit this blog regularly, you'll notice some changes to the site. For those of you that read evolgen through an RSS feed, stop by and take a look. I've widened the area allocated for posts so that they aren't forced to fit into narrow text boxes. I also added some blogs to my blogroll (which was in dire need of updating), and deleted some blogs that I either don't read much or aren't very related to the material at my site.

This was just an excuse to post this image:

Political Science

2005-11-12T07:12:00.000-05:00

Posted without comment:

Perl of Wisdom

2005-11-11T16:43:00.000-05:00

Dinosaur Comics has had guest cartoonist this past week. Today's strip takes a stab at computer science humor.

I was gonna write a joke for you using Perl scripts, but I always have so much trouble with a lot of the Perl expressions. I understand what they are supposed to do, but I can never get the syntax right.

By the way, T-REX is saying "I'm horny" and "booya" in the last panel.

Weekly Random Ten (10 November 2005)

2005-11-10T07:21:00.000-05:00

Just a Theory Edition

Toothpaste for Dinner makes me chuckle again:

Well, after what the creationists have done in Kansas, I say,

"Kansas is just a theory and shouldn't be taught in school."

When kids are required to learn about the fifty states, let's substitute Puerto Rico for Kansas. Kids won't have to learn that Topeka is the capital city of Kansas; instead, they'll be taught about San Juan. Honestly, would you rather learn about a fly over state or a tropical island? The choice is clear, Kansas is just a theory. Come on, do you know of a single person who has ever been to Kansas?

Now that I've pissed off Red State Rabble and Thoughts from Kansas, I give you this week's random ten:

Dropkick Murphys - Do or Die
Goldfinger - My Head
Catch 22 - Walking Away
David Bowie - Ziggy Stardust
Tilt - Pontiac
The Slackers - Wanted Dead or Alive
No Use For A Name - 3 Month Weekend
The Lawrence Arms - 106 South
Tiger Army - Remembered Forever
U.S. Bombs - Lunch in a Sack

Nature Blogs

2005-11-05T19:44:00.000-05:00

Check out the new Nature Genetics blog, Free Association. There aren't any posts there yet, but here's what they say is to come:

Welcome to Free Association, the Nature Genetics blog. Check here regularly for links and editorial comment on research and news in genetics, as well as reader feedback. To contact the editors directly with confidential questions or feedback, please e-mail freeassociation@natureny.com

I found the site through my StatCounter, as they link to my humble blog, along with Pharyngula, The Loom, The Intersection, and other solid science blogs. Does this mean I need to clean this place up and start putting it on my CV?

Weekly Random Ten (4 November 2005)

2005-11-04T10:09:00.000-05:00

Them Brotha's Sure Run Fast Edition

When asked why his team lost to TCU the previous Saturday, Air Force football coach Fisher DeBerry replied that TCU "had a lot more Afro-American players than we did and they ran a lot faster than we did . . . It just seems to me to be that way. Afro-American kids can run very well. That doesn't mean that Caucasian kids and other descents can't run, but it's very obvious to me that they run extremely well." DeBerry has since apologized for his statements, saying that he didn't intend to offend anyone (does anyone, really?).

The story doesn't end there, however. DeBerry has a history of -- how can I put this lightly -- offensive tendencies. And, no, these aren't due to the triple option formations that he favors. He recently removed a banner from the locker room advertising "I am a Christian first and last . . . I am a member of Team Jesus Christ" and just scrapped the pregame prayer. DeBerry's first allegiance is to Jesus, and his second is to perpetuating stereotypes. Why not just recruit speed, regardless of race? If you need faster guys to turn the corner on a sweep, move around the end and get outside contain, or track down a speedy return man, then recruit guys with sub 4.4 forty times (sorry if I lost you there with the football jargon). It seems like DeBerry has contracted a case of Paul Hornung syndrome (a recent derivative of Jimmy The Greek condition).

DeBerry isn't the only one coming down with Hornung-itous. Everyone's favorite coke-bottle-glasses wearing football coach, Joe Paterno thinks the brotha's are the reason offensive output (measured in yardage and scoring, not racist statements) has increased in the Big Ten:

"You're looking at kids from Florida, you're looking at kids from Texas, those states. They wouldn't have come to the Big Ten in the old days, probably, if there hadn't been the kind of opportunities we now have because of the practice facilities. You have to be careful the way you say things sometimes. Poor Fisher DeBerry got in trouble, but the black athlete has made a big difference. They have changed the whole tempo of the game. Black athletes have just done a great job as athletes and as people in turning the game around."

JoePa's Nittany Lions are doing well this year (compared to the last couple of seasons of futility) because they've got some solid athletes on offense. Guess where these guys come from: Maryland, Pennsylvania, and Virginia. Not a very long trip from Pennsylvania. Maybe it's due to the recent discovery that there is more to football than three yards and a cloud of dust.

Alright, I'm done playing the race card. Here's this week's Random Ten; my playlist even included one brotha' to increase speed.

Eels - Novacaine for the Soul
The Bouncing Souls - Born to Lose
The Offspring - Jennifer Lost the War
Less Than Jake - My Very Own Flag
Me First and the Gimme Gimmes - Mandy
Mad Caddies - Something's Wrong at the Playground
Ol' Dirty Bastard - Shimmy Shimmy Ya
NOFX - Three on Speed
Living End - Problem
Blink182 - Romeo and Rebecca

Science and Cinema

2005-11-04T07:51:00.000-05:00

I'm gonna chime in on this one, even though PZ Myers already has. In case you don't have access, I'm talking about the book review in Nature of Mad, Bad and Dangerous: The Scientist and the Cinema. I haven't read the book, nor do I intend to, so this is neither a review of the book, nor a review of the book review. I have my own little anecdote that I would like to share.

I caught the movie Laurel Canyon on HBO a while back, and I cringed painfully at its portrayal of a graduate student. She was at the thesis writing stage and had moved from Boston to Los Angeles with her fiance (an intern in psychiatry) to live with his mother (a sixties era rock 'n roller in the middle of producing an album for a British pop-rock band). Can't you feel the tension building? A straight-laced doctor and scientist living in a perpetual party atmosphere! I'll pause for a second, and let you wipe the drips of sarcasm from your monitor.

Apparently, the grad student is working in Drosophila genomics, although from the one requisite expository scene you would think she was studying Drah-sew-feel-ee-ah. Honestly, how hard is it to find an expert advisor to ensure the tiny bit of science in the film is presented with a semblance of accuracy? The film takes place less than ten miles from UCLA, a 15-30 minute drive depending on traffic. I’m sure they could have scrounged up a grad student from the molecular biology department to ensure that Drosophila is pronounced correctly. Pay that kid a couple hundred bucks and promise them their name in the credits, and they’ll definitely be in.

From what I remember, the way she describes her project, it sounds like she’s studying protein-protein interactions for the entire proteome, but you can’t be sure. That’s not entirely important, though. What irks me most is that the one time they pay any heed to her research they make her sound like an incompetent moron. In case you’re wondering, she is supposed to be writing her dissertation, but gets caught up in all the sex, drugs and alcohol. Her advisor keeps emailing her, and she keeps ignoring his requests for a completed draft. I would think the guy would have some hook-ups at UCLA, and could set her up with some office space there so that she could get away from the crazy party.

And if you think this is my own little issue that no one else shares, it’s not. I’ve had multiple conversations at Drosophila meetings in which this has come up amongst grad students. We all come to the same conclusion: what the hell is a Drah-sew-feel-ee-ah? It’s not a difficult word to pronounce. Say it with me, “Dro-soph-i-la”.

Tangled Bank #40

2005-11-02T13:38:00.000-05:00

Tangled Bank #40 is up at the Examining Room of Dr. Charles. Go lern yerself sum cy-ance!

The Evolution of Drosophila Non-coding DNA

2005-10-31T11:27:00.000-05:00

Peter Andolfatto's recent article on the evolution of non-coding DNA in Drosophila has elicited some comments from the blogosphere. A lot of people are referring to it as an analysis of "junk DNA," which can be traced back to this press release by UCSD and this editor's summary in Nature. I am bothered by the term "junk DNA" even when people put the scare quotes around "junk" implying they don't really mean junk or they are not sure if it really is junk. Let's just call it "non-(protein) coding DNA" and relieve it of all the associations with trash and waste.

I am going to try a new approach to commenting on a research article. I have yet to read the entire paper -- I have skimmed the abstract and looked at some of the figures -- so I am going to comment as I take a closer look at it. From what I understand, Andolfatto has looked at whole genome sequences from closely related Drosophila species and found patterns of sequence divergence and polymorphism in non-coding sequences that are not consistent with the neutral model of molecular evolution. I am hoping he can convince me that these patterns are due to selection on non-coding sequences and not demography or hitchhiking/background-selection due to selection on linked coding sequences.

Previous studies of selection on non-coding sequences has focused on conserved regulatory elements, but this approach does not allow inferences of positive selection on non-coding DNA.

"This finding suggests that taking an approach based on sequence conservation alone may lead to a biased view of regulatory evolution. Functionality of DNA sequences implies that they can be subject to both negative and positive selection. If a significant fraction of divergence between species observed in non-coding DNA is positively selected rather than selectively neutral or constrained, this could lead to underestimates of the functional importance of non-coding DNA and cause researchers to overlook the contribution of arguably the most interesting class of mutations in genome evolution -- those reflecting adaptive differences between populations and species. "

Andolfatto took a different approach toward identifying functional non-coding sequences. He looked at coding and non-coding sequences from twelve D. melanogaster individuals and one D. simulans individual from the X-chromosome. He divided the non-coding sequences into 5 classes: 5' UTRs, 3' UTRs, introns, intergenic sequences within 2kb of a gene, and intergenic sequences more than 4kb from a gene. He then calculated a variety of population genetics statistics based on these sequences to determine if any of the non-coding DNA displays signatures of natural selection. I would expect that the UTRs (sequences that are transcribed, but not translated) are under more functional constraint than the intergenic regions and probably also display more signatures of positive selection. I also would expect that the introns would be constrained and have more evidence of positive selection (due to regulatory elements located within), and that the intergenic sequences located closer to genes are under more selection than intergenic sequences further from genes.

So, what does Andolfatto's data suggest? Surprisinglyy, non-coding DNA is more conserved than silent sites within coding DNA. Silent (or synonymous) sites are nucleotides within coding sequence that can be mutated and not change the amino acid encoded by the codon due to the redundancy of the genetic code. Other research has shown that synonymous sites are under weak selection, but Andolfatto finds that the pattern of polymorphism at non-coding sites resembles that at non-synonymous sites (sites within coding sequences that when mutated lead to a codon encoding a different amino acid) more than synonymous sites. This pretty much rejects the possibility that non-coding sites display patterns of selection because they are linked to coding sequences under selection -- we would expect the same patterns observed at non-coding sites when we look at silent sites because they too would be linked to the selected sequences.

Looking at the relationship between polymorphism and divergence at the synonymous sites, non-synonymous sites, intergenic regions, introns, and UTRs, Andolfatto finds a significant excess of divergence at non-synonymous sites and UTRs. Under a neutral model, we would expect divergence to be a good predictor of the polymorphism at a locus. Too much divergence suggests that positive selection has led to the fixation of mutations in a region. This means that the non-synonymous sites and UTRs are probably under positive selection. Remember, previous studies have been able to identify purifying selection in these types of sequences, but you need the polymorphism data to infer positive selection. By doctoring the data set a bit (eliminating rare variants), Andolfatto also finds evidence for positive selection at the other non-coding sites relative to synonymous sites.

The evidence Andolfatto presents paints a picture of sequence evolution where non-coding sequences are under both selective constraint and driven to fixation by positive selection. This is consistent with regulatory regions playing as important a role in adaptive evolution as protein coding sequences. I guess the evo-devo folks have been on to something all this time, it just took a population geneticist to produce the evidence.

Andolfatto, P. 2005. Adaptive evolution of non-coding DNA in Drosophila. Nature. 437: 1149-1152.

PZ Myers Stars in Herzog Film?

2005-10-29T11:00:00.000-04:00

Has Dr. Myers's love of all things cephalopod gone too far?

For those unfamiliar, this is Werner Herzog.

Weekly Random Ten (28 October 2005)

2005-10-28T13:26:00.000-04:00

Back on Friday Edition

Yes, the random ten is back for a special Friday edition. Of course, next week it may be on Tuesday or Thursday, so stay tuned.

Right now I'm in the middle of writing about some experiments I've done and some that I plan to do. Yes, it's (grant) proposal writing time! I've got a proposal for my thesis committee due on Monday for a meeting the following week. I don't have a problem writing the background and motivations, and the preliminary results and analysis aren't too bad either. Some of my results are in preparation for publication, and other results are getting there; I just need to write a brief summary and include a couple of figures and tables.

It's the data analysis for data I don't even have that really gets to me. I fell like its just a string of conditional statements -- if my data looks like this, it would mean this, and then I would do this. Otherwise, I would do this, and it would mean this. If it looks like this, I'll scratch my head and ask my advisor what I should do next. I didn't actually write that last part . . . the idea did go through my, though. Figuring out how to write about data analyses that I've never done leaves me unsure if any of the proposed data analysis makes sense. Luckily, I can co-opt some of the stuff from this proposal for my real grant proposal that's due in a couple of weeks. Plus, I'm hoping to get some good comments from my committee that may lead to a stronger grant proposal.

The bitching is done for now, so on to the evolgen Weekly Random Ten. Let's see if these tunes can help me get through the proposal writing process (this week, with comments).

Less Than Lake - Showbiz? Science? Who Cares? [Sounds like the Kansas Kangaroo Kourt.]
311 - Amber [Like that stuff they found with the dinosaur DNA in Jurassic Park.]
Bombshell Rocks - Microphone [Sounds like . . . a Rancid knock off.]
Bouncing Souls - The Ballad of Johnny X [Hey, it's my favorite band that can't play their instruments.]
Sugar Ray - RPM [That nice Mark McGrath named a song after me.]
Tilt - Clothes Horse [It seems likes there's a Tilt song on each random ten.]
NOFX - Drugs are Good [Hard to disagree with that.]
The Used - Lunacy Fringe [Is that the new name for the religious right?]
Me First and the Gimme Gimmes - Country Roads [Greatest. Cover band. Ever.]
The Distillers - Idoless [An Aussie band for John Wilkins.]